Biomedical subjects

C Whitney

Publications and source records attributed to C Whitney.

At least 37 records · Page 2Linked to original sources

PubMed1994

Thrombocytosis in surgically treated stage IB squamous cell cervical carcinoma (A Gynecologic Oncology Group study).

Thrombocytosis has previously been shown to be an unfavorable prognostic factor in cervical cancer patients treated with irradiation. We evaluated the significance of thrombocytosis (platelet count > 400 x 10(9)/liter in 623 surgically treated patients with stage IB squamous cell carcinoma of the cervix. These patients had no gross evidence of extrauterine disease at the time of exploration, and none had metastasis to the para-aortic nodes. Fifty-nine (9.5%) of these 623 patients had thrombocytosis. The 5-year survival for patients with thrombocytosis was 82% compared to 83.5% for patients with normal platelet count (P = 0.4). Pelvic node metastasis was present in 13 (22%) of 59 patients with thrombocytosis, and 77 (13.7%) of 564 patients with normal platelet count (P = 0.1). There was a significant correlation between tumor size and platelet count. Patients with thrombocytosis had a mean tumor size of 27.9 mm, while it was 20.4 mm in patients without thrombocytosis (P = 0.002). Other factors found to be associated with thrombocytosis in this population were elevated white blood cell (WBC) count (P = 0.009) and history of chronic obstructive pulmonary disease (COPD) (P = 0.02). In a multivariate analysis for thrombocytosis adjusted for COPD, WBC count, and tumor size, tumor size continued to be statistically significant (P = 0.01). These data suggest that thrombocytosis is a marker of tumor burden and not an independent prognostic factor for progression-free interval or survival.

Adult↗

PubMed1994

Effect of treatment on titer, function, and antigen recognition of serum antibodies to Actinobacillus actinomycetemcomitans in patients with rapidly progressive periodontitis.

Although periodontal treatment by scaling and root planing (SCRP) is known to induce bacteremia, the effect of this procedure on the host immune response is not known. We have determined pre- and post-SCRP immunoglobulin G antibody titers to antigens of Actinobacillus actinomycetemcomitans in the sera of 22 patients with rapidly progressive periodontitis. We also assessed the ability of these sera to enhance phagocytosis and killing of A. actinomycetemcomitans by human polymorphonuclear leukocytes by using a polymorphonuclear leukocyte chemiluminescence (CL) assay. Specific anti-A. actinomycetemcomitans antibody titers were significantly increased at 6 and 12 months after beginning treatment, and CL values were significantly increased at 12 months, whereas mean interproximal pocket depths were significantly decreased at 12 months after beginning treatment. When patients were classified as either seropositive (twice the median titer of control subjects; n = 10) or seronegative (n = 12), both median titers and CL values were significantly increased for the seronegative group at 6 and 12 months after treatment. In the seropositive group, only the median titer was significantly increased at 12 months. Western blot (immunoblot) patterns for six seronegative and six seropositive patients differed remarkably at the baseline. Before treatment, all of the seropositive patients recognized high-molecular-mass lipopolysaccharide (LPS) and a large number of protein components. Patterns were virtually unaffected by therapy. Before treatment, only one of the seronegative patients recognized the LPS smear and none reacted strongly with protein components. Following treatment, slight LPS staining was observed for five of six seronegative patients and detection of protein bands was enhanced in all cases. We conclude that treatment by SCRP induces a humoral immune response, especially in seronegative patients, and that response may play a role in the observed beneficial effects of periodontal treatment.

Adult↗

PubMed1994

Immunization against Porphyromonas gingivalis inhibits progression of experimental periodontitis in nonhuman primates.

Periodontitis is a common infectious disease in which the attachment tissues of the teeth and their alveolar bone housing are destroyed, resulting in tooth loss. The gram-negative anaerobic microorganism Porphyromonas gingivalis has been closely linked to severe forms of the disease. We show for the first time that immunization of the primate Macaca fascicularis with killed P. gingivalis in Syntex Adjuvant Formulation-M inhibits progression of periodontal tissue destruction.

Animals↗

PubMed1994

Malpractice claims during 1988-1992: a national survey of dentists.

Between 1988 and 1992, almost a quarter of surveyed dentists reported at least one patient complaint to malpractice insurance carriers. The incidence of claims more than doubled in that time and payment size increased nearly five times between 1988 and 1991. These and other trends in professional liability are examined in this national survey of general dentists.

Age Factors↗

PubMed1994

Dental malpractice liability insurance market: surveys of insurers and insurance commissioners.

Surveys of malpractice insurers and state insurance commissioners in 1992 show a highly concentrated market with opportunities for greater competition. Fewer than 50 firms write coverage nationally. Weighted premiums for $1 million/$3 million coverage vary across U.S. census divisions from $1,700 in the South to $3,000 in the Northeast. These data may be of interest to practitioners who purchase insurance and will aid dental associations in effectively participating in revisions of malpractice liability statutes as part of overall health care reform.

Data Collection↗

PubMed1994

Topical anesthesia: differentiating the pharmacological and psychological contributions to efficacy.

Pain can be influenced by both pharmacologic and psychologic factors. The purpose of this study was to investigate the pharmacologic and psychologic factors. The purpose of this study was to investigate the pharmacologic and psychologic processes that may play a role when topical anesthesia is used to reduce the pain of dental injections. Subjects were assigned to one of two belief manipulation conditions: one-half of the subjects were led to believe they would receive a placebo, while the remaining subjects were told they would receive the active agent. In reality, all subjects received two separate injections at contralateral sites, one preceded by a placebo and the other by a 20% benzocaine gel. The order in which injections were given was associated with differences in pain report. Second injections were more painful than first injections. Whether injections were preceded by an active or placebo agent did not alter subjects' experienced pain. Likewise, the belief manipulation did not affect the pain report. However, subjects who believed they would receive the active agent anticipated significantly less pain than subjects who thought they would receive placebo. The widespread belief that topical anesthetics are effective at reducing injection pain may serve to reduce the anticipatory anxiety associated with an impending dental injection, thus making the injection experience less aversive.

Administration, Topical↗

PubMed1993

Selenium regulation of glutathione peroxidase in human hepatoma cell line Hep3B.

Glutathione peroxidase is an important enzyme in cellular antioxidant defense systems, detoxifying peroxides and hydroperoxides. As a component of the glutathione cycle, it protects the liver from reactive oxygen metabolites. Selenocysteine is present at the catalytic site of glutathione peroxidase, and selenium availability regulates glutathione peroxidase enzyme activity. Hep3B cells, a well-differentiated human hepatoma-derived cell line, exhibited time-dependent decrease in glutathione peroxidase activity (nmol NADPH oxidized/min/mg protein, mean +/- SE) when incubated in selenium-free medium for 10 days (Day 0, 21.8 +/- 7.3; Day 2, 10.9 +/- 1.2; Day 4, 7.9 +/- 0.8; Day 6, 4.0 +/- 0.7; Day 8, 4.5 +/- 0.6; Day 10, 1.6 +/- 0.4). With the reintroduction of selenium, glutathione peroxidase activity returned. A second human hepatoma cell line, HepG2, demonstrated a similar pattern when depleted of and then repleted with selenium. To assess protein synthesis, glutathione peroxidase activity was measured in deficient and replete Hep3B cells incubated with and without selenium and with and without cycloheximide. Deficient cells (mean +/- SE) (4.9 +/- 0.2) showed an increase in glutathione peroxidase activity after 24 h in selenium-containing medium (11.6 +/- 0.2), but not when cycloheximide was included in the medium (6.9 +/- 0.5) or when cycloheximide and no selenium was included (5.3 +/- 0.8). Replete Hep3B cells (40.1 +/- 1.1) demonstrated decreased glutathione peroxidase after 24 h in medium without selenium (34.0 +/- 1.4), medium with both cycloheximide and selenium (34.0 +/- 2.6), and medium without selenium and containing cycloheximide (37.6 +/- 1.3). These data suggest that protein synthesis is needed for selenium repletion to exert control on glutathione peroxidase activity. Using a cDNA for human glutathione peroxidase (GPx1), selenium-deficient and replete Hep3B cell RNA was analyzed by Northern blot. mRNA for GPx was quantified by densitometry. The steady-state mRNA level for glutathione peroxidase in deficient cells was 40% of that in replete cells. Nuclear run-on studies to determine the rate of GPx-specific mRNA synthesis showed no difference between nuclei from selenium-replete and selenium-deficient cells. This finding eliminated the possibility of differential transcription rates as an explanation for the observed reduction in mRNA brought about by selenium deficiency and suggested instead a stabilization of mRNA in selenium-replete cells. While selenium deficiency decreased mRNA levels by 60%, glutathione peroxidase enzyme activity decreased by 93%, suggesting a co- and/or post-translational control mechanism in addition to the effect on mRNA stability.

Carcinoma, Hepatocellular↗

PubMed1992

Opsonic antibody activity against Actinobacillus actinomycetemcomitans in patients with rapidly progressive periodontitis.

Actinobacillus actinomycetemcomitans has been closely associated with early-onset, severe periodontitis, and such patients often have serum immunoglobulin G (IgG) antibodies reactive with antigens of this gram-negative pathogen. We examined the functionality and potential importance of these antibodies. The opsonic activity against A. actinomycetemcomitans of sera from 30 patients with rapidly progressive periodontitis (RPP) and from 28 periodontally normal subjects was tested by using polymorphonuclear leukocyte (PMN) chemiluminescence and bactericidal assays. Peak chemiluminescence values correlated strongly with killing observed in the PMN-dependent bactericidal assay (r = 0.88; P < 0.001). Neither the mean IgG titer nor the mean peak chemiluminescence differed significantly between the two groups. However, when the relationship between chemiluminescence and titer was examined, regression analysis showed that antibodies present in low-titer normal sera were significantly more effective at opsonizing A. actinomycetemcomitans than antibodies present in low-titer RPP patient sera (P = 0.04). Thus, periodontally normal individuals may be better able than RPP patients to clear A. actinomycetemcomitans in early stages of colonization, and anti-A. actinomycetemcomitans antibodies in RPP patients may be relatively ineffective in preventing infection by this organism.

Adult↗

PubMed1992

Serum immunoglobulin G antibody to Porphyromonas gingivalis in rapidly progressive periodontitis: titer, avidity, and subclass distribution.

Porphyromonas gingivalis is a suspected pathogen in rapidly progressive periodontitis (RPP). We have determined the anti-P. gingivalis serum immunoglobulin G (IgG) isotype response and avidity and the subclass titer distributions for 30 RPP patients and 30 age-, sex-, and race-matched healthy subjects by using enzyme-linked immunosorbent assay technology. Patients and control subjects were classified as seropositive if their total IgG response to P. gingivalis was twofold or more than the median response in healthy subjects. The predominant antibody responses for both patients and healthy subjects were IgG2 and IgG3, with a subclass order of IgG2 greater than IgG3 greater than IgG1 greater than IgG4. The avidity of the IgG response was highest for the seropositive healthy subjects and was no different between seronegative and seropositive RPP patients. The subclass antibody responses did not depend on gender, and there were no correlations between titer, avidity, or subclass with disease severity in the RPP patients as measured by pocket depth or bone loss on dental X rays. The seronegative RPP patients exhibited antibody responses that were greater than the responses of seronegative healthy subjects for all four subclasses, while the seropositive RPP patients had higher IgG1 and IgG4 levels than seropositive healthy subjects. These findings are consistent with the hypothesis that both carbohydrate and protein antigens are important in the IgG response to P. gingivalis. The relative predominance of IgG2, a subclass which lacks strong complement fixation and opsonic properties, and the low avidity of patient anti-P. gingivalis IgG antibodies suggest that humoral responsiveness to infection with P. gingivalis may be ineffective in clearing this organism.

Adolescent↗

PubMed1991

In vitro regulation of human phagocyte cytochrome b heavy and light chain gene expression by bacterial lipopolysaccharide and recombinant human cytokines.

We examined the effects of bacterial lipopolysaccharide and several recombinant human cytokines (tumor necrosis factor alpha and granulocyte-, macrophage-, and granulocyte-macrophage colony-stimulating factors) on the expression of the genes for the phagocyte cytochrome b, an essential component of the superoxide-generating oxidase. In vitro treatment with lipopolysaccharide, tumor necrosis factor alpha, or macrophage- or granulocyte-macrophage colony-stimulating factors increased the levels of transcripts for the cytochrome b heavy chain (gp91phox) 9- to 22-fold and transcripts for the light chain (p22phox) 2- to 5-fold in cultured human monocyte-derived macrophages. The same agents, except for macrophage colony-stimulating factor, induced the expression of the cytochrome b heavy chain gene 2- to 12-fold and light chain gene 2- to 6-fold in human granulocytes. The expression of the cytochrome b heavy and light chain genes was coordinated in both macrophages and neutrophils with regard to stimulus specificity and dose-response pattern. The time course for induction of the two genes was parallel in both cell types for all stimuli. The macrophage response to lipopolysaccharide occurred at least in part at the transcriptional level. These results show that a variety of physiological regulators modulate the coordinated expression of the cytochrome b genes.

Blotting, Northern↗

PubMed1991

Severe cyanide poisoning from the ingestion of an acetonitrile-containing cosmetic.

A 39-year-old woman ingested 59 mL of Super Nail Nail Off (American International Industries, Hollywood, CA) (containing 99% acetonitrile) in a suicide attempt. Following a latent period of approximately 12 hours, the patient developed cyanide poisoning with severe metabolic acidosis, seizures, and shallow respirations. She responded to the administration of sodium nitrite and sodium thiosulfate, although the administration of nitrite produced bradycardia and hypotension. She developed several relapses over the course of her hospitalization and each time responded to sodium thiosulfate administration. The patient developed hypernatremia from the sodium load given to her; hemodialysis and charcoal hemoperfusion were initiated to correct the hypernatremia and to attempt to remove cyanide, thiocyanate, and acetonitrile. On the fifth hospital day, the patient was fully recovered and was discharged.

Acetonitriles↗

PubMed1989

Post-transcriptional regulation of glutathione peroxidase gene expression by selenium in the HL-60 human myeloid cell line.

We have used a cloned cDNA for the major human selenoprotein, glutathione peroxidase (GPx), to assess the mode of regulation of human GPx gene (GPX-1) expression by selenium. When the HL-60 human myeloid cell line is grown in a selenium-deficient medium, GPx enzymatic activity decreases 30-fold compared with selenium-replete cells. Upon return to a medium containing selenium in the form of selenite, GPx activity in the cells starts to increase within 48 hours and reaches maximal (selenium-replete) levels at 7 days. Steady-state immunoreactive protein levels correlate with enzymatic activity. Cycloheximide inhibits the rise in GPx activity that accompanies selenium replenishment, indicating that protein synthesis is required for the increase. However, GPx mRNA levels and the rate of transcription of the human GPx gene change very little and thus appear to be independent of the selenium supply. Thus the human GPx gene appears to be regulated post-transcriptionally, probably cotranslationally, in response to selenium availability.

Blotting, Western↗

PubMed1989

Differentiation of human hematopoietic cells increases expression of a gene transferred by a retroviral vector.

To study expression of a retroviral vector in human hematopoietic lineages, two established human hematopoietic cell lines (HL60 and K562) and a human adherent stromal cell line (KM101) were infected with the vector pZIP-SV(X). Expression of the transferred neomycin resistance gene (neor) of pZIP-SV(X) was evaluated as the ability of the cells to form colonies (greater than 50 cells) in an agar assay in the presence of the neomycin analogue, G418. After infection, all three cell lines produced colonies resistant to G418. The level of neor mRNA in separate colonies was analyzed by Northern blot analysis. The neor gene transferred by the vector pZIP-SV(X) was expressed in both human hematopoietic and stromal cell lines. In addition, primary adherent human stromal cells infected with pZIP-SV(X) grew in the presence of G418. To determine if differentiation of hematopoietic cells affects expression of the retroviral vector, HL60 cells infected with pZIP-SV(X) were induced to differentiate, and the level of neor mRNA measured. The amount of neor mRNA increased when HL60 cells were induced to differentiate along the granulocytic pathway. Conversely, when HL60 cells were induced toward monocytoid differentiation (TPA), the level of neor mRNA did not significantly increase. We conclude that the neor gene transferred by a retroviral vector, pZIP-SV(X), is functionally expressed. In addition, expression of the transferred neor gene is regulated during myeloid differentiation of HL60 cells.

Cell Differentiation↗

PubMed1989

Use of CA 125 to monitor patients with ovarian epithelial carcinomas.

The CA 125 radioimmunoassay has been increasingly used to monitor the course of patients with ovarian epithelial carcinomas. The purpose of this report is to describe our experience in the use of this assay and to better define its clinical utility. Fifty-one patients had serum CA 125 follow-up during primary chemotherapy. All 51 patients demonstrated either a normal CA 125 level at the completion of chemotherapy or a substantial fall in CA 125 values with treatment. In 48 of 51 patients, the drop in CA 125 levels was temporally related to the clinical regression or remission of tumor. Forty of these patients underwent second-look laparotomy; 23 patients (58%) had residual disease. A total of 45 patients had serum CA 125 determinations at the time of second-look laparotomy. Eight patients with microscopic disease and 11 of 18 patients with gross residual disease had a "negative" (less than 35 U/ml) CA 125 level. The predictive value of an elevated CA 125 level was 1.00. However, the predictive value of a negative value was only 0.50. Hence, a negative CA 125 level cannot be a substitute for a second-look laparotomy. Only 7 of 18 patients (39%) with gross residual disease at second-look surgery had an elevated CA 125 level. Patients with an elevated CA 125 and gross residual tumor at the second-look laparotomy uniformly demonstrated large, bulky disease. Furthermore, the survival of patients with gross residual disease at second-look laparotomy correlated with the preoperative CA 125 value. Serum CA 125 determinations also show promise in the follow-up of patients with a negative second-look laparotomy. The serum CA 125 level from patients with a "negative" second-look laparotomy can become elevated months before recurrent disease is appreciated.

Actuarial Analysis↗

PubMed1988

Induction of phagocyte cytochrome b heavy chain gene expression by interferon gamma.

Phagocytic cells, such as macrophages and polymorphonuclear leukocytes, produce a "respiratory burst" in which oxygen is reduced to superoxide and other active oxygen species responsible for many of the microbicidal, tumoricidal, and inflammatory activities of these cells. Interferon gamma has been shown to augment phagocyte superoxide production, but the molecular mechanisms underlying this effect have remained unknown. Recently a key component of the oxidase, phagocyte cytochrome b, has been characterized as a heterodimer of a 91-kDa glycoprotein and a 22-kDa polypeptide. The present studies examined the effects of human recombinant interferon gamma on the expression of the genes for these components of the cytochrome b. In vitro treatment with interferon gamma substantially increases the level of phagocyte cytochrome b heavy chain gene transcripts in normal polymorphonuclear leukocytes, normal monocyte-derived macrophages, and the monocytic leukemia cell line THP-1. Light chain gene transcripts are less affected. In monocyte-derived macrophages and THP-1 cells, the enhanced expression of the heavy chain gene appears in large part attributable to increased rates of transcription. Treatment of monocyte-derived macrophages with human recombinant interferon alpha (a down-regulator of the respiratory burst) decreased the heavy chain transcript levels; interferon beta produced no detectable change. These findings demonstrate the responsiveness of one essential component of the phagocyte oxidase system to activation by interferon gamma and provide a rationale for its use to augment phagocytic function in chronic granulomatous disease.

Cytochrome b Group↗

PubMed1987

Positive groin lymph nodes in superficial squamous cell vulvar cancer. A Gynecologic Oncology Group Study.

The term microinvasive carcinoma is inappropriate when applied to all vulvar cancers less than or equal to 5 mm thick because approximately 50% of vulvar carcinomas are no thicker than 5 mm and 20% of those superficial tumors metastasize to the lymph nodes. The significant predictors of groin node metastases in patients with superficial vulvar cancer are tumor thickness, histologic grade (proportion of undifferentiated tumor pattern), capillary-like space involvement with the tumor, clitoral or perineal location, and clinically suspicious nodes, according to the linear logistic model analysis of clinicopathologic data in 272 women. No lymph node metastases occurred in approximately one fourth of patients with a combination of low-risk factors: no clinically suspicious nodes, negative capillary-like space, and nonmidline vulvar cancers that were either grade 1 and 1 to 5 mm thick or grade 2 and 1 to 2 mm thick. In contrast, all 10 patients with clinically suspicious nodes and grade 4 tumors had positive groin nodes. The risk of lymph node metastases is best determined by simultaneous evaluation of all risk factors rather than a single factor such as tumor thickness.

Carcinoma, Squamous Cell↗

PubMed1987

Morphometric analysis of endometrial adenocarcinoma: 1. Does architectural dedifferentiation accompany deep invasion by endometrial adenocarcinoma?

Important prognostic factors for endometrial adenocarcinoma include histologic differentiation, depth of myometrial invasion, and clinical stage. Deep myometrial penetration is more commonly observed with poorly differentiated carcinomas, but it is unknown if these tumors are poorly differentiated de novo, or if selection toward more aggressive, less differentiated cells occurs during invasion. To study this question, we performed a morphometric analysis to quantitate the amount of glandular differentiation in superficial portions of 22 endometrial carcinomas for comparison with deep portions of the same neoplasm. Point counting of randomly selected fields was performed on histologic sections of hysterectomy specimens of 22 women with stage I endometrial adenocarcinoma. The components enumerated were tumor cells participating in gland formation (DI), non-gland-forming tumor cells (UI), tumor gland lumens (LUM), inflammatory cells (IC), and stroma (endometrium or myometrium) (ST). Slides of tumors were divided into superficial, middle, and deep thirds. No statistically significant differences were seen between superficial and deep thirds (UI: 45% vs. 43%; DI: 33% vs. 32%; LUM: 22% vs. 24%; IC: 3% vs. 3% of points counted, p greater than .1, paired t-test). The density of tumor cells relative to stroma was greater in the superficial region (55% vs. 41%, p less than .001, paired t-test). Additionally, field-to-field heterogeneity was examined by four methods. No relationship between increased heterogeneity and poor prognosis was identified. These findings do not support the concept that invasion by endometrial adenocarcinoma is accompanied by architectural dedifferentiation.

Adenocarcinoma↗

PubMed1987

Morphometric analysis of endometrial adenocarcinoma: 2. A comparison of architectural differentiation determined morphometrically with subjective grading.

Architectural differentiation is the primary criterion used in the grading of endometrial adenocarcinomas. However, there is little evidence supporting the accuracy of pathologists' assignment of histologic grade, and few studies on the value of architectural morphometry in predicting prognosis for endometrial adenocarcinoma. We have thus investigated whether a pathologist's estimate of percentage of tumor in solid array correlated with the volume fraction of tumors composed of cells not participating in gland formation determined morphometrically. Additionally, we conducted this morphometric study of 31 cases of Stage I endometrial cancer to determine the relationship between a variety of objective measurements of architectural arrangement and prognosis. We found that a pathologist can accurately estimate the proportion of endometrial tumors arranged in solid or glandular fashion. In this limited study, morphometric assessment of the proportion of differentiated or undifferentiated cells or lumens did not improve the accuracy of prediction of outcome beyond conventional architectural grading. Further, we reaffirm that estimation of architectural arrangement coupled with measurement of the depth of penetration provides a good index of the probability of survival.

Adenocarcinoma↗