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Biomedical subjects

K Welch

Publications and source records attributed to K Welch.

At least 37 records · Page 2Linked to original sources
PubMed1997

Scavenger receptors are present on rabbit aortic endothelial cells in vivo.

Endothelial cells metabolize modified LDL, but attempts to detect scavenger receptors in this cell type in vitro have been unsuccessful. To determine whether scavenger receptors are present on endothelial cells in vivo, species-specific reagents were developed to detect rabbit scavenger receptor protein. Antiserum against the rabbit scavenger receptor was generated with the use of synthetic peptides of two distinct regions: residues 3 to 21 in the cytoplasmic tail and residues 282 to 304 in the collagen-like region. Reactivity of antiserum against the synthetic peptides was confirmed with an enzyme-linked immunosorbent assay. Positive reactivity was also observed against fragments of scavenger receptor protein expressed in bacteria. Antiserum to both regions reacted with liver membrane proteins of sizes consistent with the scavenger receptor, as confirmed by Western blotting under reduced and nonreduced conditions. Immunocytochemical examination of rabbit aortic tissue by use of antiserum to both regions of scavenger receptor protein produced striking and identical patterns of staining of aortic endothelium. Immunostaining was abolished for both antisera by preadsorption with the specific peptide region used as immunogen. In contrast, incubation of scavenger receptor antiserum with a peptide of a region of the rabbit LDL receptor failed to influence immunoreactivity against endothelium. These data demonstrate the presence of scavenger receptors in rabbit endothelium in vivo, which may have fundamental implications for lipoprotein metabolism by the arterial wall.

Amino Acid Sequence↗
PubMed1997

Expression of p53 protein in actinic keratosis, adjacent, normal-appearing, and non-sun-exposed human skin.

Nonmelanoma skin cancer, including both squamous cell carcinoma and basal cell carcinoma, is a significant and increasing health problem in the United States. The precursor lesion of cutaneous squamous cell carcinoma, actinic keratosis (AK), is a major risk factor for nonmelanoma skin cancer, and it is also a marker of long-term sun exposure. AKs themselves can serve as biomarkers in chemopreventive studies, but in addition, they may contain phenotypic and genetic alterations that are related to the process of UV-induced skin carcinogenesis. One of these alterations, the tumor suppressor gene p53, is altered early in UV-induced skin carcinogenesis in humans. p53 protein expression was measured by immunohistochemistry in biopsies from AKs, tissue immediately adjacent to AKs (AK-adjacent), normal-appearing upper medial arm skin, and non-sun-exposed skin from 19 subjects. There was a significant difference and a progressively increasing mean p53 labeling index in total epidermis (basal and suprabasal layers) between upper medial arm skin (0.9 +/- 1.8%) and AK-adjacent (12.1 +/- 14.4%; P = 0.0004) and between AK (27.7 +/- 21.3%) and AK-adjacent skin (P = 0.04), whereas upper medial arm skin was marginally different from non-sun-exposed skin (0.1 +/- 0.2; P = 0.05). This pattern of p53 expression was also seen when epidermis was separated into basal and suprabasal layers. We conclude that epidermal p53 protein expression is associated with histological evidence of chronic sun damage.

Aged↗
PubMed1996

Disposition and metabolism of topically administered alpha-tocopherol acetate: a common ingredient of commercially available sunscreens and cosmetics.

Skin cancers are a serious health problem in the United States. One common method of skin cancer primary prevention is use of sunscreens. Research has been conducted to ascertain the role of active ingredients of sunscreen products in photoprotection and possible carcinogenesis. In contrast, little is known about the "other ingredients", listed or unlisted, on sunscreen product labels. One such ingredient is vitamin E. usually in the form of alpha-tocopherol acetate. Results of recent studies of skin carcinogenesis in an ultraviolet (UV) B mouse carcinogenesis model suggest that topically applied alpha-tocopherol acetate does not prevent and, under some conditions, enhances skin cancer development and growth, whereas the free unesterified from of alpha-tocopherol significantly reduces experimental UVB carcinogenesis. We have performed a Phase II cancer prevention study to evaluate whether topically applied alpha-tocopherol acetate is absorbed in human skin and metabolizes to the free or other forms. In this double-blind study, 19 men and women > 30 years of age who had at least three actinic keratoses on their forearms were randomly assigned to apply alpha-tocopherol acetate (125 mg/g) or difluoromethylornithine cream to their arms twice daily for three months. Blood samples and photographs and punch biopsies of actinic keratoses were obtained before and at the end of the study (Month 4). Plasma and skin concentrations of free alpha-tocopherol, alpha-tocopherol acetate, and gamma-tocopherol were analyzed by high-performance liquid chromatography at Month 4. The results of this report focus only on data obtained from the 11 participants randomized to the alpha-tocopherol acetate arm of the study. Topically applied alpha-tocopherol acetate was substantially absorbed in skin, with no evidence of conversion within skin to its unesterified form (i.e., free alpha-tocopherol). There was no evidence of systemic availability or biotransformation of topically applied alpha-tocopherol acetate. In summary, we have determined that alpha-tocopherol acetate is not metabolized to the free form of alpha-tocopherol in plasma or skin.

Administration, Topical↗
PubMed1996

Mouse peritoneal macrophages contain abundant omega-6 lipoxygenase activity that is independent of interleukin-4.

The action of an omega-6 lipoxygenase (LO) has been implicated in the development of atherosclerosis through a mechanism involving oxidation of LDL, and its regulation in macrophages may have important implications for the disease process. Human monocyte-derived macrophages (HMDMs) showed no demonstrable LO protein or activity unless they were incubated with interleukin-4 (IL-4). In contrast, mouse peritoneal macrophages (MPMs) possessed significant basal levels of LO activity and protein that were augmented by IL-4 treatment. Interferon gamma prevented the induction of LO in both HMDMs and MPMs. Whereas interferon gamma could completely block the IL-4 induction of LO in human cells, it did not suppress basal LO activity in MPMs. Both HMDMs and MPMs exhibited similar concentration-response relationships for stimulation of LO activity and protein, with maximal induction at 1 ng/mL IL-4. The time course of IL-4 induction of LO activity was markedly different in human and murine cells. IL-4 induced LO activity and protein in human cells by 48 hours that were maximal by 72 hours; there was a decline to a new baseline by 96 hours. MPMs have a significant amount of LO activity at baseline, which declined with time by nearly 10-fold in the absence of IL-4, IL-4 blunted the decline of LO activity with time and restored activity to that found at baseline by 48 hours. IL-4 was not responsible for the LO activity present in freshly isolated MPMs since both activity and protein content were similar in cells harvested from IL-4+/+ and IL-/- mice. Therefore, whereas IL-4 may be an important modulator of LO production in vitro, it is not essential for the in vivo expression of this protein. Further, these studies demonstrate that significant differences exist between monocyte-derived macrophages matured in vitro and tissue macrophages that have matured in vivo.

Animals↗
PubMed1996

The first year of hyperinflation in the former Soviet Union: nutritional deprivation among elderly pensioners, 1992.

OBJECTIVES: Hyperinflation began in early 1992 in the former Soviet Union. This paper describes factors associated with nutritional status that year among elderly pensioners. METHODS: Approximately 300 pensioners were selected randomly in each of eight cities. Surveys of diet, weight, health status, and social and economic conditions were done between June and December 1992. This paper reports on 2281 completed questionnaires. RESULTS: Half the pensioners reported that they had lost 5 or more kilograms in the prior 6 months; 57% did not have enough money to buy food, and 39% needed medicines they could not afford. Forty percent consumed less than a half kilogram of meat, 50% consumed less than a half kilogram of fruit, a third consumed less than a liter of milk, and a third consumed less than 2 kg of bread per week. Weight loss was strongly associated with not having enough money to buy food, and inability to afford medication, and consumption of fewer than three meals a day. Concurrent with these conditions, there was a large increase in mortality in Russia. CONCLUSIONS: The results of these surveys suggest that many elderly pensioners were experiencing severe nutritional deprivation in the latter half of 1992.

Aged↗
PubMed1996

Health and nutrition in children under 2 years of age in three areas of the Russian Federation.

The study objectives were to determine the nutritional status of children under 2 years of age in selected areas of the Russian Federation, to estimate the proportion of children potentially at risk for nutritional problems, and to characterize such a vulnerable group in terms of demographic variables. A cross-sectional sample of children under 2 years of age was used. Six areas-Moscow, St Petersburg, Ekaterinburg, and their surrounding oblasts-were sampled, and data were collected for approximately 800 children in each area between July and December 1993. A low prevalence of children with a weight-for-age Z-score below -2 was found, indicating that at the time of the survey protein-energy malnutrition was not a serious problem for this age group. However, other survey results indicating high morbidity, low immunization rates, the possibility of food insecurity, and poor infant-feeding practices imply that children's health could easily deteriorate. Therefore, food security and children's nutrition should be monitored to avoid serious consequences in the future. The results also show that there is ample scope for public health interventions that encourage more effective immunization coverage, emphasize prevention of childhood diseases, and promote proper infant-feeding practices.

Adult↗
PubMed1996

Evaluation of proliferating cell nuclear antigen as a surrogate end point biomarker in actinic keratosis and adjacent, normal-appearing, and non-sun-exposed human skin samples.

The incidence of nonmelanoma skin cancer, including both squamous cell carcinoma and basal cell carcinoma, is a significant health problem in the United States. Actinic keratosis (AK), the precursor of cutaneous squamous cell carcinoma, is a major risk factor for nonmelanoma skin cancer. In addition, AKs are tissue targets for the identification of biomarkers for use in chemopreventive studies. The biomarker addressed in this study is epidermal cell proliferation, as quantitated by proliferating cell nuclear antigen (PCNA). Shave biopsies were obtained from AKs, tissue immediately adjacent to AKs, normal-appearing, upper-medial arm skin, and non-sun-exposed skin from 19 subjects. When any degree of PCNA staining was considered positive (semiquantitative 1-4 scale), there was a significant difference and a progressively increasing mean PCNA labeling index (LI) in the total epidermis (basal and suprabasal layers), beginning with non-sun-exposed buttock skin, with the lowest LI (2.5 + or - 1.6%), followed by upper-medial arm skin (12.3 + or - 7.4%; P = 0.0015), skin adjacent to AKs (19.2 + or - 12.2%; P = 0.0218), and finally, AKs with the highest LI (34.6 + or - 20.1%; P = 0.0017). This same pattern was observed when the epidermis was separated into basal and suprabasal layers, with the exception of a nonsignificant result for upper-medial arm skin compared with adjacent skin in the basal layer (P = 0.3981). PCNA LIs were also analyzed separately by staining intensity (i.e., scores of 1-4). The PCNA LI in skin with varying degrees of sun damage and/or histological atypia is a candidate surrogate end point biomarker for skin cancer chemoprevention studies.

Aged↗
PubMed1995

Performance of the Gen-Probe amplified Mycobacterium tuberculosis direct test in a laboratory that infrequently isolates Mycobacterium tuberculosis.

The performance of the Gen-Probe Mycobacterium tuberculosis direct (MTD) test was assessed in a laboratory whose specimens were derived from a population with a low prevalence (1.3%) of tuberculosis. A total of 339 specimens from 113 patients were included in the study. Nine of 10 MTD positive samples were culture positive (smear positive, n = 7; smear negative, n = 1; smear not ordered, n = 2). The 10th MTD-positive sample, which was smear and culture negative, was from a patient whose two other study specimens were smear and culture positive and who had a clinical history consistent with tuberculosis. Prior to and following resolution of discrepant results, the sensitivities and specificities of the MTD test relative to culture were 100 and 99.7% and 100 and 100%, respectively.

Bacteriological Techniques↗
PubMed1994

Antibacterial activity of sucralfate versus aluminum chloride in simulated gastric fluid.

Studies have previously demonstrated that sucralfate possesses intrinsic antibacterial activity. This study was designed to indirectly assess whether aluminum is the active antibacterial component of sucralfate and to further evaluate factors that may influence this agent's antibacterial activity. Utilizing an in vitro model, the antibacterial activity of sucralfate, an equivalent quantity of aluminum in the form of aluminum chloride, and a control were compared. In addition, the influences of bacterial species (Enterobacter cloacae and Pseudomonas aeruginosa), time (0-24 h) and environmental pH (3,5,7) on the agents' antibacterial activities were evaluated. Equivalent quantities of aluminum, as either sucralfate or aluminum chloride, were added to two of three flasks containing approximately 10(5) cfu/ml of bacteria in pH-adjusted simulated gastric fluid. The third flask served as a control. Samples were obtained over 24 h, diluted and subcultured onto agar plates. The experiments demonstrated that bacterial growth was influenced by pH, time and treatment (aluminum chloride or sucralfate). Regardless of pH or bacterial species, bacterial death occurred within 20 min following the addition of aluminum chloride. In contrast, bacterial death following the addition of sucralfate was more variable and appeared to be pH dependent. In conclusion, sucralfate and aluminum chloride both possess antibacterial activity, even at pH values that normally support bacterial growth in gastric fluid. Although differences in the antibacterial activity of the two agents may in part be related to drug-induced changes in pH, these differences also support data suggesting that aluminum release from sucralfate is incomplete and is dependent on pH.

Aluminum↗
PubMed1994

Characterization of CD34+HLA-DR-CD38+ and CD34+HLA-DR-CD38- progenitor cells from human umbilical cord blood.

In this study we show that depletion of cells expressing mature cell markers, including HLA-DR, followed by positive cell sorting for cells expressing CD34 and CD38, can be used to define functionally distinct hematopoietic cells from human umbilical cord blood (HUCB). The CD34+HLA-DR-CD38+ population contained the majority of directly clonogenic cells, while the optimal ability to maintain long term co-culture with bone marrow stromal cells was present within the CD34+HLA-DR-CD38- population. 1.2 +/- 0.4% of the CD34+HLA-DR-CD38- cells plated at 1 cell/well and grown in the presence of hematopoietic growth factors (HGF) formed hemopoietic colonies. Mesenchymal elements were observed in 20% of these cultures. No cell growth, however, was observed when the CD34+HLA-DR-CD38- cells were cultured in the absence of HGF. This is in contrast with the findings in fetal bone marrow which demonstrated the presence of stem cells that were independent of HGF. Thus, while it is possible to isolate very immature hemopoietic progenitor cells from HUCB defined by the phenotype Lin-CD34+HLA-DR-CD38-, these cells do not appear to exhibit the pluripotentiality of the analogous population reported in fetal bone marrow. We conclude that these cells are absent or at a very small frequency in HUCB.

ADP-ribosyl Cyclase↗
PubMed1993

A novel cellular model (SPGM 1) of switching between the pre-B cell and myelomonocytic lineages.

The suspension pro granulocyte/macrophage (SPGM1) cell line was established from a transplantable mouse progranulocytic/promacrophage tumor. Surprisingly, SPGM1 cells expressed a typical CD5 pre-B cell phenotype, being positive for Ly-1 (CD5), PB76, B220 (CD45RA), and the pre-B Ig receptor complex (microH chains, lambda 5 and vpre-B surrogate L chains, and the IgM alpha (mb-1) and Ig beta (B29) co-receptor molecules). Southern Blot analysis revealed clonal rearrangement of the microH chain locus and germ-line L chain loci. SPGM1 formed blast cell-, macrophage-, and occasional granulocytic colonies in soft agar in the presence of murine IL-3. IL-3 also induced macrophage differentiation of SPGM1 cells in suspension cultures. The earliest changes were detectable at 24 h by Northern blot analysis. IL-3-treatment increased Mac1 mRNA, induced c-fms mRNA, and down-regulated mRNA for mu, lambda 5, vpre-B and mb-1. After 2 to 4 days the cells were larger, strongly adherent, expressed the macrophage markers Mac1 and F4/80, had lost microH chain and PB76 surface expression, and readily phagocytosed latex beads. Thus SPGM1 has all the characteristic features of a CD5+ pre-B cell line. However, IL-3 predominantly induced SPGM1 to switch its differentiation program from a pre-B cell to a macrophage. This inducible, rapid switch of virtually the entire population provides a unique model for the molecular analysis of mechanisms involved in cell-fate determination.

Animals↗
PubMed1993

Bullous pemphigoid and autoimmunity.

BACKGROUND: There are many case reports of bullous pemphigoid (BP) in association with a variety of autoimmune disorders, but no large case controlled studies have been performed. OBJECTIVE: Our purpose was to determine whether there is an increased incidence of autoimmune disorders in patients with BP and whether there is a particular haplotype associated with this. METHODS: A total of 108 patients with BP were studied and compared with a group of 108 age- and sex-matched controls. HLA typing at the A, B, C, and DR loci was performed on 55 of the 108 patients with BP. RESULTS: The difference in incidence of autoimmune disorders between patients and controls was not significant. The haplotypes of patients with BP were similar to those of a locally drawn population. CONCLUSION: There is no increase in the incidence of autoimmune disorders in BP, and no particular haplotype appears to be associated with a predisposition to this condition.

Aged↗
PubMed1992

Isolation and characterization of a novel receptor-type protein tyrosine kinase (hek) from a human pre-B cell line.

In this report we describe the identification and characterization of a novel tumor-associated receptor-type tyrosine kinase (hek). We produced a monoclonal antibody (III.A4) that detected a novel glycoprotein on the immunizing pre-B cell acute lymphoblastic leukemia cell line (LK63). This antigen was shown to be expressed sporadically on hemopoietic tumor cell lines and on ex vivo tumors. However, using antibody staining, the molecule was undetectable on normal tissues. Further biochemical characterization showed this molecule (hek) to be a phosphoroprotein. This observation taken together with the tumor-associated nature of hek expression suggested that hek might be a receptor-type protein tyrosine kinase. This was demonstrated by affinity purification of hek. In in vitro kinase experiments the purified hek protein was autophosphorylated on tyrosine and also mediated tyrosine phosphorylation of casein. Purified hek was subjected to N-terminal amino acid sequence analysis which showed that hek had a unique N terminus. Amino acid sequence determination of peptides from a V8 protease digest of hek yielded one 21-amino acid stretch of sequence which showed close homology with the eph subfamily of protein tyrosine kinases. These studies show hek to be a novel human tumor-associated protein tyrosine kinase, which by analogy with previously characterized protein tyrosine kinase proto-oncogenes, may have a role in tumorigenesis.

Amino Acid Sequence↗
PubMed1992

Temporal lobectomy for complex partial seizures that began in childhood.

Forty-six consecutive patients who underwent surgery for intractable temporal lobe seizures originating in childhood are reported; invasive preoperative monitoring (e.g., depth electrodes and subdural arrays) was not used in the selection process. Our results, with respect to the control of seizures and improvement in behavior, are comparable to those of series in which invasive monitoring was used in the selection process. Eighty-five percent of the 46 patients (96% of the 28 operated after the introduction of long-term electroencephalographic monitoring) became either seizure free or experienced near total control of their seizures. Our results indicate that many patients can be selected successfully for temporal resection without exposure to the risk and expense of invasive presurgical procedures. A long duration of epilepsy prior to surgery in patients with neoplasia portended a less satisfactory outcome. Our results strengthen the argument for early operation in children with intractable epilepsy.

Adaptation, Psychological↗
PubMed1992

Sumatriptan.

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History, 20th Century↗
PubMed1992

Prevalence of tumor prevention rather than tumor enhancement when repetitive UV radiation treatments precede initiation and promotion.

UV irradiation can act as a tumor initiator in mouse skin, yet repetitive UV irradiation can systemically prevent chemically induced two-stage skin tumorigenesis. The present study addressed the question of whether repetitive dorsal UV irradiation would enhance or inhibit subsequent initiation and promotion applied dorsally. Approximately 4.25 x 10(5) J/m2 was applied intermittently to 30 shaved CDF1 mice over an 8 week period. Mice were then initiated dorsally with 100 micrograms of 7,12-dimethylbenz[a]anthracene and subsequently promoted with 7.5 micrograms 12-O-tetradecanoylphorbol-13-acetate (TPA) applied twice weekly for 19 weeks. Initiated and promoted mice that had been treated repetitively with 1.06 x 10(4) J/m2 showed a decrease in tumor incidence from 92 to 28%, and a reduction in tumor yield per mouse from 5.35 to 0.58, at 19 weeks after the first TPA treatment. Histological analysis revealed that the UVB radiation treatments used in these experiments did not produce permanent loss of epidermal cells or sebaceous gland atrophy. When the same dose of UVB irradiation was applied after initiation and promotion, no increased conversion of papillomas to carcinomas was found, within a 48 weeks experimental duration. Thus, repetitive UV irradiation prevented rather than enhanced subsequent two-stage tumorigenesis. Repetitive UVB irradiation at late stages of promotion failed to enhance conversion of papillomas to carcinomas within the time frame in which chemical initiators mediate conversion to malignancy.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Cerebral hemicorticectomy for epilepsy.

Hemicorticectomy resulted in total or near-total control of seizures in 10 of 11 children with chronic epilepsy. During a median follow-up period of 5.5 years, there have been no deaths or delayed complications. The surgical outcome after hemicorticectomy compares favorably with that of more extensive surgical procedures, yet is associated with significantly less risk. The technique for hemicorticectomy is described and illustrated.

Adolescent↗