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Biomedical subjects

A J Katz

Publications and source records attributed to A J Katz.

At least 19 recordsLinked to original sources
PubMed2004

Genetic and cellular mechanisms in chromium and nickel carcinogenesis considering epidemiologic findings.

Genetic and environmental interactions determine cancer risks but some cancer incidence is primarily a result of inherited genetic deficits alone. Most cancers have an occupational, viral, nutritional, behavioral or iatrogenic etiology. Cancer can sometimes be controlled through broad public health interventions including industrial hygiene and engineering controls. Chromium and nickel are two human carcinogens associated with industrial exposures where public health measures apparently work. Carcinogenic mechanisms of these metals are examined by electron-spin-resonance-spectroscopy and somatic-mutation-and-recombination in Drosophila melanogaster in this report. Both metals primarily affect initiation processes in cancer development suggesting important theoretical approaches to prevention and followup.

Animals↗
PubMed2003

Mesenchymal stem cells from rat visceral fat exhibit multipotential differentiation in vitro.

Human subcutaneous fat-derived stem cells were recently shown to have the potential to differentiate in vitro into a variety of cell types, including adipocytes, osteoblasts, chondrocytes, and myoblasts (Zuk et al., Tissue Eng. 2001;7:211-228). Subcutaneous adipose tissue may therefore prove to be an easily acquired and abundant source of stem cells. Presently it is unclear whether mammals such as rats (which possess small or nonexistent subcutaneous fat pads) contain mesenchymal stem cells within the visceral fat of the abdominal cavity, or whether the visceral fat of any species contains stem cells. In this study we isolated and expanded a pool of mesenchymal cells from visceral fat of adult Sprague-Dawley rats and induced their differentiation in vitro into adipocytes, osteoblasts, neural cells, and chondrocytes. The differentiated phenotypes were verified by morphology as well as detection and expression of tissue-specific protein and mRNA. We conclude that despite well-documented differences in the metabolic and biochemical properties among anatomically distinct depots of fat, the visceral fat of rats contains adult mesenchymal stem cells with developmental potential similar to those isolated from subcutaneous fat in humans. Therefore, animals such as rats provide both a source of fat-derived stem cells and an immunocompetent, autologous host animal in which to investigate the capacity of the fat-derived cells to differentiate and form tissues in vivo.

Adipocytes↗
PubMed2001

Combining Drosophila melanogaster somatic-mutation-recombination and electron-spin-resonance-spectroscopy data to interpret epidemiologic observations on chromium carcinogenicity.

Lung cancers are significantly increased among workers exposed to chromate (Cr6+, Cr3+), chromium pigments (Cr6+) and chromium plating (Cr6+). Chromium lung burdens and cancer risk increase proportionately with duration of employment at long latencies. However, this epidemiologic information alone is insufficient in determining whether Cr6+ or Cr3+ are equally important in causing cancer. We have attempted to combine epidemiologic data with data from the Drosophila melanogaster somatic-mutation-recombination-test and from the in vitro electron-spin-resonance spectroscopy study to demonstrate that following somatic recombination plays a more important role than somatic mutation in chromium carcinogenesis. Cr4+ is more important than Cr5+ or Cr6+ in inducing somatic recombination while Cr6+ produces more and bigger clones than Cr4+ in somatic mutation. Cr3+ produces negative results in this fruit-fly wing-spot-assay. When the larvae and flies exposed to Cr6+ and Cr4+ are examined by ESR, only Cr5+ and Cr3+ are found. Thermodynamic parameters deltaE, deltaH, and deltaS are also estimated from these latter experiments to explain the relative importance of Cr6+, Cr4+, Cr3+ in chromium carcinogenesis among exposed industrial workers.

Animals↗
PubMed2001

Multilineage cells from human adipose tissue: implications for cell-based therapies.

Future cell-based therapies such as tissue engineering will benefit from a source of autologous pluripotent stem cells. For mesodermal tissue engineering, one such source of cells is the bone marrow stroma. The bone marrow compartment contains several cell populations, including mesenchymal stem cells (MSCs) that are capable of differentiating into adipogenic, osteogenic, chondrogenic, and myogenic cells. However, autologous bone marrow procurement has potential limitations. An alternate source of autologous adult stem cells that is obtainable in large quantities, under local anesthesia, with minimal discomfort would be advantageous. In this study, we determined if a population of stem cells could be isolated from human adipose tissue. Human adipose tissue, obtained by suction-assisted lipectomy (i.e., liposuction), was processed to obtain a fibroblast-like population of cells or a processed lipoaspirate (PLA). These PLA cells can be maintained in vitro for extended periods with stable population doubling and low levels of senescence. Immunofluorescence and flow cytometry show that the majority of PLA cells are of mesodermal or mesenchymal origin with low levels of contaminating pericytes, endothelial cells, and smooth muscle cells. Finally, PLA cells differentiate in vitro into adipogenic, chondrogenic, myogenic, and osteogenic cells in the presence of lineage-specific induction factors. In conclusion, the data support the hypothesis that a human lipoaspirate contains multipotent cells and may represent an alternative stem cell source to bone marrow-derived MSCs.

Adipocytes↗
PubMed2001

A novel device for the simple and efficient refinement of liposuctioned tissue.

In short, our device allows a surgeon who is harvesting adipose tissue for autologous fat transplantation to immediately, easily, efficiently, and sterilely isolate adipose tissue from the unwanted waste components that are associated with primary liposuction effluent. It does so by "trapping" the fat tissue contained within raw liposuction effluent. Once the tissue fraction has been separated, the device design then allows for direct implantation or subsequent washing/rinsing of the tissue with saline/buffer of choice in preparation for tissue reimplantation.

Adipose Tissue↗
PubMed2000

Prospective analysis suggests susceptibility genes for deficiencies of IgA and several other immunoglobulins on the [HLA-B8, SC01, DR3] conserved extended haplotype.

The extended major histocompatibility complex (MHC) haplotype [HLA-B8, SC01, DR3] is increased in frequency among patients with immunoglobulin (Ig)A deficiency and common variable immunodeficiency. Because the genomic region from HLA-B to HLA-DR/DQ is virtually the same on all instances of the haplotype in the general population, we reasoned that all independent instances of [HLA-B8, SC01, DR3] carry MHC susceptibility genes for these disorders. To define immunoglobulin deficiencies determined by genes on this haplotype and their mode of expression and penetrance, serum immunoglobulin class and IgG subclass concentrations were determined prospectively in homozygotes and heterozygotes of this haplotype and in Caucasian controls. Prevalence of individual immunoglobulin deficiencies in persons with [HLA-B8, SC01, DR3] ranged from 13% to 37%, significantly higher than rates in non-carriers or general controls. We found significantly increased frequencies of IgA and IgG4 deficiency only in homozygotes (13.3% and 30%, respectively) compared with heterozygotes (1.7% and 3.4%) or non-carriers (1.6% each), suggesting recessive expression. In contrast, IgD and IgG3 deficiencies were significantly more common in both homozygotes (36.7% and 30%) and heterozygotes (20.3% and 17.5%) compared with controls (4.9% and 3.4%), suggesting dominant inheritance. These results indicate multiple distinct susceptibility genes, some recessive and others dominant, for deficiency of IgA, IgD, IgG3 or IgG4 (but not for IgE, IgG1, IgG2 or IgM) on [HLA-B8, SC01, DR3]. These observations may also help to explain the observed associations of [HLA-B8, SC01, DR3] with both IgA deficiency and common variable immunodeficiency and the common occurrence of IgG subclass deficiencies in some patients with IgA deficiency.

Common Variable Immunodeficiency↗
PubMed1999

Emerging approaches to the tissue engineering of fat.

The eventual development of tissue-engineered fat equivalents for reconstructive and augmentation purposes will be most welcome by nearly every surgical discipline and prove to be especially useful for plastic surgeons. The clinical applications for which tissue-engineered fat will be particularly useful are vast and varied and can be loosely categorized into reconstructive, cosmetic, corrective, and orthotic indications. In this article, the authors discuss the emerging tissue-engineering strategies for fat, including the procurement of autologous cells, cell growth and differentiation, implantation and engraftment, polymer scaffolds, and implant integration and histogenesis.

Adipocytes↗
PubMed1998

Modulation by temperature of the genotoxic potency of cisplatin in Drosophila wing spot assay.

Effects of temperature on genotoxic potency of cisplatin were studied in the Drosophila wing spot assay. A fixed concentration of 0.05 mM cisplatin was evaluated for genotoxicity at 4 temperatures (18, 20, 25, and 29 degrees C). The compound was found to be a positive inducer of all three endpoints at all temperatures when compared to the water controls. While no effect of temperature was found on the percentages of cisplatin-treated wings with small spots, there were significant effects for large spots and twin spots. The capacity of cisplatin to induce both large spots and twin spots tended to increase with rising temperature. A significant linear regression was obtained in regard to temperature and number of cisplatin-induced large spots per wing. The lack of any effect of temperature on induced small spots provides additional evidence that small spots may be qualitatively different from large spots and twin spots. The observed enhancement by higher temperature of cisplatin's genotoxic potency is likely due in part to increased cellular uptake of the mutagen. Wide temperature fluctuations should be avoided when conducting the wing assay. Although the customary temperature for performing the assay has been within the range 24-25 degrees C, the optimum temperature for maximizing genotoxic potency (and sensitivity of the assay) may be nearer 27 degrees C.

Animals↗
PubMed1997

Inhibition of peripheral blood mononuclear cell proliferation by cardiac glycosides.

INTRODUCTION: Prior studies have shown that ouabain, a cardiac glycoside that inhibits the sodium, potassium adenosine triphosphatase (Na+,K+ ATPase) enzyme, downregulates phytohemagglutinin (PHA)-induced peripheral blood mononuclear cell (PBMNC) proliferation. OBJECTIVE: This study examined and compared the effects of both ouabain and digoxin, a cardiac glycoside used therapeutically in humans, on PBMNC proliferation. METHODS: Peripheral blood mononuclear cells were isolated from healthy human subjects, incubated for 72 hours with and without PHA (2%) in the presence and absence of ouabain (10(-12) M to 10(-4) M) or digoxin (10(-9) M to 10(-6) M), and pulsed with 3H thymidine. RESULTS: For PHA-stimulated PBMNCs in the ouabain-treated group (n = 10 subjects), the mean (+/-STD) % uptake (% 3H thymidine uptake in absence of ouabain) was 80.5 +/- 6.0 at 10(-12) M ouabain, 73.1 +/- 8.4 at 10(-10) M, 47.89 +/- 13.1 at 10(-8) M, 6.9 +/- 3.2 at 10(-6) M, and 3.4 +/- 1.6 at 10(-4) M. For PHA-stimulated cells in the digoxin-treated group (n = 9 subjects), the mean (+/-STD) % uptake (% 3H thymidine uptake in absence of digoxin) was 89.8 +/- 9.8 at 10(-9) M digoxin, 92.6 +/- 8.2 at 10(-8) M, 54.3 +/- 19.8 at 10(-7) M, and 1.0 +/- 2.4 at 10(-6) M. Repeated measures ANOVA demonstrated a significant effect of concentration of both glycosides on PBMNC proliferation (P < .01). The inhibitory effect was reversible, but was largely abbrogated if ouabain was added after 48 hours of incubation with PHA. Further, the inhibitory effect extended to PBMNCs stimulated with recall antigen (tetanus) and to fractionated PBMNCs (CD4+, CD8+ and CD19+) stimulated with mitogens. Additionally, dose-response inhibitory effects of glycosides on PBMNC Na+,K+ ATPase enzyme activity and interleukin-2 (IL-2) secretion by PHA-stimulated PBMNC were also noted. Neither glycoside had an effect on spontaneous PBMNC proliferation (no PHA) or trypan blue exclusion. CONCLUSIONS: These studies demonstrate that both cardiac glycosides inhibited PHA-induced PBMNC proliferation, possibly via Na+,K+ ATPase inhibition, but not via cell toxicity. The concentration range over which inhibition was observed was similar for both glycosides. The results raise the possibility that therapeutic or toxic doses of digoxin could have an effect on cell-mediated immunity in vivo.

Adult↗
PubMed1995

Comparison of bacteria growth in single and pooled platelet concentrates after deliberate inoculation and storage.

BACKGROUND: The ability to store pools of platelet concentrates (PCs) for extended periods would provide logistical flexibility. However, reports of severe adverse reactions due to the transfusion of contaminated PCs led to an examination of whether the total bacteria levels after storage of pools containing a deliberately inoculated platelet unit would be significantly different than the levels in paired unpooled concentrates. STUDY DESIGN AND METHODS: A single PC was deliberately inoculated on Day 0 with one of three bacterial species (0.1-8.0 colony-forming units/mL). On Day 1, the deliberately inoculated PC was divided into three equal parts and either 1) pooled with 5 half-volume, ABO- and Rh-identical PCs; 2) similarly pooled and white cell reduced; or 3) kept as a control. Sterile connections were used during pooling; modified storage containers were used to ensure the correct surface-to-volume ratio of the single unit. RESULTS: Between Day 2 and Day 5 of storage, in 26 of 36 paired samples, nonfiltered pools containing Escherichia coli had greater total numbers of bacteria than did the paired single PCs. Day 2 pools had total bacteria levels approximately five times higher (colony-forming units/mL x container volume) than those in single units (p < 0.05). There was rapid growth of Staphylococcus aureus by Day 2 in pooled and unpooled PCs; by Day 3, total bacteria levels were approximately five times higher in pools than in single units (p < 0.05). Between Days 3 and 5 of storage, in 23 of 27 paired samples, nonfiltered pools containing S. aureus had greater total bacteria levels than the single PCs. By Day 5, 15 of 16 non-white-cell reduced pools had total levels of Staphylococcus epidermidis bacteria approximately five times those in the paired single PCs. Greater total bacteria levels in pooled units than in single units generally occurred when bacteria in pools reached the stationary phase of growth (when bacteria concentration became constant), and they were well correlated with the sixfold volume of pooled units. White cell reduction did not substantially affect the time required to attain stationary phase. CONCLUSION: The potential during storage for greater total bacteria levels in pools than in single PCs is a consequence of the greater volume of the pool.

Bacteria↗
PubMed1993

Major histocompatibility complex susceptibility genes for dermatitis herpetiformis compared with those for gluten-sensitive enteropathy.

Dermatitis herpetiformis (DH) shares some clinical features and major histocompatibility complex (MHC) markers with gluten-sensitive enteropathy (GSE). We compared MHC haplotypes in 27 patients with DH, 35 patients with GSE, and normal controls. As in GSE, the frequencies of two extended haplotypes, [HLA-B8, SC01, DR3] and [HLA-B44, FC31, DR7], were increased in patients with DH. Distributions of fragments of extended haplotypes, consisting of some but not all of the elements of complete extended haplotypes, were analyzed to attempt to localize a susceptibility gene. Besides complete extended susceptibility haplotypes, (DR3, DQ2) and (DR7, DQ2) fragments were most common in GSE. In contrast, DH showed only a few such fragments but many instances of the fragment (SC01). The differences in distribution of these fragments in the two diseases were highly significant (P < 0.002). HLA-DQ2 and DR3 had the highest odds ratios for GSE, but the highest odds ratio for DH was for the complotype SC01. These findings suggest that the MHC susceptibility gene for DH is between class II and complotype regions, closest to the complotype, whereas that for GSE is in the class II region.

Celiac Disease↗
PubMed1993

Effect of temperature on frequencies of spots in Drosophila wing-spot assay.

The effect of temperature on spontaneous mutation frequencies was studied in the Drosophila somatic mutation and recombination test. Transdihybrid mwh +/+ flr3 larvae were grown at various temperatures (15, 18, 20, 22, 25, 27, and 29 degrees C) in the absence of any chemical mutagen. Wings of surviving adults were removed and scored for presence of small single spots, large single spots, and twin spots. No significant effect of temperature was found on mean frequency per wing of twin spots. Similarly, no significant effect of temperature was found for large singles within the temperature range of 18-29 degrees C; however, at 15 degrees C, the mean frequency per wing of large spots was significantly elevated. A significant quadratic relationship was found between mean frequency of small spots and temperature. Frequency of small spots per wing was minimized within the temperature range of 20-27 degrees C and increased at higher and lower temperatures. Maximum frequency of small spots per wing was observed at 15 degrees C. The qualitative nature of the small single spots induced at high and low temperatures is unclear; they may represent slow-growing segmentally aneuploid (deleted) cells or possibly even monosomic cells. Both heat and cold were found to be mutagenic in the Drosophila wing-spot assay. However, the mutagenic potency associated with temperature was much less than that of most chemical mutagens, and no significant effect of temperature was observed in the range of 20-27 degrees C.

Animals↗
PubMed1992

Tetracycline-induced esophagitis in adolescent patients.

Ulcerative esophagitis may be caused by corrosive agents and by commonly prescribed medications. We report severe esophagitis in five adolescents after ingestion of tetracycline preparations with minimal water immediately before going to bed.

Adolescent↗
PubMed1992

Relationship of common laboratory parameters to the activity of Crohn's disease in children.

The Pediatric Crohn's Disease Activity Index (PCDAI) has been proposed as a simple instrument to aid in the classification of patients by disease severity. The PCDAI includes subjective patient reporting of symptoms, physical examination, nutritional parameters, and several common laboratory tests (hematocrit, erythrocyte sedimentation rate, albumin). In this report we examine the relationship of each of the laboratory parameters to the PCDAI, as well as to a modified Harvey-Bradshaw Index score and physician global assessment of disease activity. Data were gathered from the clinical and laboratory observations from 133 children and adolescents at 12 pediatric gastroenterology centers in North America. A statistically significant relationship (p less than 0.05) was noted between each of the laboratory tests and the PCDAI for patients with either disease limited to the small bowel or in those with colonic involvement. For patients with disease limited to the small bowel, a statistically significant (p less than 0.05) relationship was also noted between the three laboratory parameters and the modified Harvey-Bradshaw Index and global assessment. For patients with large-bowel involvement, the erythrocyte sedimentation rate was statistically related to the modified Harvey-Bradshaw Index and global assessment (p less than 0.01), as was hematocrit to global assessment (p less than 0.01). Although the laboratory parameters used in the PCDAI appear to generally reflect disease activity in most patients, no single laboratory test is adequate to reflect disease activity in all patients. Future work will need to identify additional laboratory measures to reflect the inflammatory process and serve as important adjuncts in the assessment of disease activity.

Adolescent↗
PubMed1991

Development and validation of a pediatric Crohn's disease activity index.

Clinical and laboratory observations of 133 children and adolescents with Crohn's disease were used to validate an index of severity of illness previously developed by a group of senior pediatric gastroenterologists at a research forum in April 1990. This pediatric Crohn's disease activity index (PCDAI) included (a) subjective reporting of the degree of abdominal pain, stool pattern, and general well-being; (b) presence of extraintestinal manifestations, such as fever, arthritis, rash, and uveitis; (c) physical examination findings; (d) weight and height; and (e) hematocrit, erythrocyte sedimentation rate, and serum albumin. Independent evaluation of each patient by two physician-observers was performed at the time of a visit, and each physician completed a PCDAI index and a modified Harvey-Bradshaw index and made a "global assessment" of disease activity as none, mild, moderate, or severe. Excellent interobserver agreement was noted for the PCDAI, modified Harvey-Bradshaw index, and global assessment. There was a strong correlation between global assessment and both the PCDAI or modified Harvey-Bradshaw. Increasing PCDAI scores were noted with increasing disease severity, and significant differences in scores were noted between the severity groups. We propose that the PCDAI could be used in multicenter projects to facilitate patient stratification by disease severity and that longitudinal PCDAI scores might provide a numerical measure of response to therapeutic regimens.

Adolescent↗
PubMed1989

Genetic prediction of nonresponse to hepatitis B vaccine.

In previous studies of the antibody response to hepatitis B vaccine in 598 subjects who received a full course of vaccination, we observed a bimodal response, with about 14 percent producing less than approximately 1000 radioimmunoassay (RIA) units. An analysis of the major histocompatibility complex (MHC) HLA and complement types of 20 of the subjects with the lowest responses indicated a greater-than-expected number of homozygotes for the extended or fixed MHC haplotype [HLA-B8, SC01, DR3]. This finding suggested that the lack of a normal response was a recessive MHC-linked trait. In this study, we prospectively vaccinated five homozygotes and nine heterozygotes for this haplotype in the expectation that the homozygotes would produce much lower levels of antibody than the heterozygotes. When the antibody response was assessed two months after the third injection, four of the five homozygotes had produced very low levels (approximately 1000 units or less) of antibody (mean, 467 RIA units; range, less than 8 to 1266), whereas all nine heterozygotes produced more than 2500 RIA units (mean, 15,608; range, 2655 to 28,900) (P less than 0.01). We conclude that the usual response to hepatitis B surface antigen is due to the presence of a dominant immune-response gene in the MHC and that a low response is due to the absence of such a gene and the presence on both chromosomes of MHC haplotypes (such as [HLA-B8, SC01, DR3]) that indicate such a response.

Adolescent↗
PubMed1989

Sodium thiosulfate inhibits cisplatin-induced mutagenesis in somatic tissue of Drosophila.

The antitumor agent cisplatin was evaluated for genotoxicity in the somatic tissue of Drosophila melanogaster in combination with the nucleophilic compound sodium thiosulfate (STS). Third instar larvae transheterozygous for mwh and flr3 were grown on media containing (1) water, (2) 200 mM STS, (3) 0.05 mM cisplatin in 200 mM STS, or (4) 0.05 mM cisplatin. Wings of surviving adults were scored for the presence of twin spots and both small and large single spots; 200 mM STS was nongenotoxic in the assay. Whereas 0.05 mM cisplatin significantly induced all three endpoints, 0.05 mM cisplatin in combination with 200 mM STS was found to have no genotoxic activity. Hence, STS possessed antimutagenic activity in the wing-spot assay and completely inhibited cisplatin-induced mutagenesis and mitotic recombination.

Animals↗