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G A Miller

Publications and source records attributed to G A Miller.

At least 73 records · Page 4Linked to original sources
PubMed1996

Studies of proliferative responses by long-term-cryopreserved peripheral blood mononuclear cells to bacterial components associated with periodontitis.

Freezing techniques provide a means for repeating and extending immunological assays with frozen aliquots of an individual's peripheral blood mononuclear cell fraction. Lymphocytes which are stored frozen for a limited time retain their ability to respond to polyclonal B-cell activators, mitogens, and antigens of dental interest. Our studies extend these previous findings by determining lymphocyte functional activity following frozen storage for up to 100 weeks. In addition, the autologous immune response was measured by spontaneous lymphocyte proliferation following 0, 1, 40, and 60 weeks of frozen storage. Peak responses for all individuals occurred at day 7 of incubation. The lymphocyte proliferative response to the superantigens toxic shock syndrome toxin-1 (TSST-1) and Staphylococcus enterotoxin A (SEA) were not changed after 100 weeks of frozen storage. Maximum responses varied among the individuals but occurred at equivalent stimulator concentrations. However, slopes generated from data obtained following 0, 4, 13, 20, 30, 50, 88, and 100 weeks of frozen storage showed no significant deviation from zero (P > 0.05) for all individuals tested. After 100 weeks of storage, the total changes in proliferative activity (counts per minute per week) were -2.1% +/- 16.8% and -5.5% +/- 17.0% for TSST-1 and SEA, respectively. The lymphocyte proliferative responses to pokeweed mitogen, concanavalin A, and sonicates of two periodontal pathogens (Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans) following frozen storage were similar to those with TSST-1 and SEA. These results indicate that peripheral blood mononuclear cells stored frozen may serve as appropriate controls to monitor changes in the disease state long-term periodontal treatment.

Aggregatibacter actinomycetemcomitans↗
PubMed1996

Immunomodulatory and superantigen activities of bacteria associated with adult periodontitis.

Immune dysfunctions are frequently associated with chronic inflammatory diseases. Several investigators have reported that patients with severe periodontitis show reduced or negligible levels of proliferative responses of peripheral blood and gingival lymphocytes to periodontopathic organisms. The purpose of this study was to evaluate the influences of products from Porphyromonas gingivalis (P. gingivalis) and Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) on lymphocytes obtained from periodontally diseased and non-diseased individuals in order to extend our understanding of the possible role of such bacterial components as immune modulators. Pooled cultures of either P. gingivalis or A. actinomycetemcomitans were disrupted using glass beads in a bead mill to prepare whole cell homogenates. These homogenates were then co-cultured with human peripheral blood mononuclear cells (PBMC) and known lymphocyte stimulators. Cultures were pulsed with tritiated thymidine, harvested, and radio label incorporation was determined. Responses to toxic shock syndrome toxin-1 (TSST-1) and pokeweed mitogen (PWM) were inhibited at high concentrations of bacterial homogenate. However, as the concentration was reduced, responses induced by PWM were restored while TSST-1 induced responses remained inhibited. Such results suggest that P. gingivalis and A. actinomycetemcomitans contain potent immunosuppressants with differential influences on lymphocyte population. These effects on B- and T-cells are independent of periodontal disease status and appear to exert their influence through non-toxic mechanisms. In addition, work currently underway presently indicates that obligate oral anaerobic bacteria such as P. gingivalis produce substances with some of the characteristics of superantigens.

Adult↗
PubMed1996

Tumor proliferative activity is predictive of pathological stage in clinical stage A nonseminomatous testicular germ cell tumors.

PURPOSE: Traditional histopathological features have failed to predict accurately the pathological stage of clinical stage A nonseminomatous germ cell tumors of the testis. Based on pilot studies in nonconsecutive patients at our university, we evaluated nontraditional risk factors (cell cycle analysis by flow cytometry, deoxyribonucleic acid analysis by single cell cytophotometry [image analysis] and assessment of proliferative activity by immunohistochemistry) combined with histopathological features in consecutive patients with clinical stage A nonseminomatous testis cancer. MATERIALS AND METHODS: Orchiectomy specimens from 105 consecutive patients with clinical stage A nonseminomatous germ cell tumors who underwent retroperitoneal lymph node dissection (76 with pathological stage A disease and 29 with proved metastasis) were recut, histopathologically reviewed, immunohistochemically stained with proliferation markers (for example Ki-67/MIB-1), and examined by flow cytometry and image analysis. RESULTS: After multiple logistic regression analysis, the G2M+S cell cycle fraction of the aneuploid tumor stemline was the most predictive parameter of pathological stage (p = 0.0004). Using a cutoff of 41%, patients with metastasis were predicted with a sensitivity of 71%. Of 61 patients with a G2M+S value of less than 41%, 53 had pathological stage A cancer (negative predictive value 87%). A low volume of embryonal carcinoma was predominant in patients at low risk for metastasis and MIB-1 immunohistochemical staining identified 23% of patients with pathological stage A tumor who were at extremely low risk for metastatic disease. CONCLUSIONS: Assessment of tumor cell proliferation cannot classify accurately high risk patients at a clinically applicable level. However, identification of patients at low risk for metastasis by flow cytometry, immunohistochemical proliferation markers and volume of embryonal carcinoma may be possible at the 90% level. MIB-1 staining is able to classify patients at extremely low risk for metastasis. These parameters deserve further study, since identification of patients at extremely low risk for metastasis could potentially decrease overall morbidity in the management of clinical stage A nonseminomatous testis cancer.

Cell Division↗
PubMed1996

The role of flow cytometric DNA analysis in determining prognosis of resectable ductal adenocarcinoma of the pancreas.

Carcinoma of the pancreas is a leading cause of cancer mortality in the United States. Improvement in prediction of survival is needed. Flow cytometric analysis as a prognostic tool has produced conflicting results. We retrospectively analyzed the clinicopathologic features, operative factors, and outcome of 39 curative resections for ductal adenocarcinoma of the head of the pancreas performed at Indiana University Medical Center between 1989 and 1994. The group was composed of 20 females and 19 males. Procedures performed were Whipple without vagotomy (n = 5), Whipple with vagotomy (n = 19), pylorus-preserving Whipple (n = 12) and total pancreatectomy (n = 3). Thirty-two tumors were suitable for DNA analysis. Of the 32 patients with flow cytometric data, 33 per cent (3/9) of living patients and 39 per cent (9/23) of deceased patients had aneuploid tumors (P = 0.999). The average S-phase for living patients was 8.3 per cent +/- 3.8 per cent, and 16.1 per cent +/- 13.6 per cent for deceased patients (P = 0.115). In the multivariate analysis, only lymphatic invasion (P = 0.015) and alkaline phosphatase level (P = 0.024) predicted poor survival. Our data show no correlation between flow cytometric DNA ploidy, S-phase analysis, and prognosis in patients undergoing curative resection for ductal adenocarcinoma of the pancreatic head.

Adenocarcinoma↗
PubMed1996

Relationship of preoperative serum CA-125 to survival in epithelial ovarian carcinoma.

BACKGROUND: Epithelial carcinoma of the ovary has the highest death rate of any gynecologic malignancy in the developed world. The antigen CA-125 has been used over the past decade as a tumor marker for epithelial ovarian cancer and other cancers of coelomic epithelium. The object of this study was to see if the degree of elevation of preoperative CA-125 was related to length of survival in patients with epithelial ovarian carcinoma. METHODS: Eighty-two consecutive patients diagnosed with epithelial ovarian carcinoma were evaluated for their initial preoperative CA-125 level, time to recurrence, length of survival and level of primary debulking as well as International Federation of Gynecologists and Obstetricians stage, grade and histology. Ovarian tumors of low malignant potential were not included in the study. All patients had their initial surgery performed by one surgeon. RESULTS: Decreased length of survival was related to the degree of elevation of CA-125 prior to initial exploratory laparotomy (P = .047). The mean initial CA-125 for patients surviving five years or more (15 patients) was 899 U/mL, with an SD of +/- 1,880 U/mL, while the CA-125 for patients surviving less than five years (67 patients) was 1,978 U/mL, with an SD of +/- 1,852 U/mL (P = .02). Increased stage of disease at initial laparotomy showed a relationship to increased CA-125 (P < .0001). CONCLUSION: In epithelial ovarian carcinoma, high preoperative serum levels of CA-125 predict decreased length of survival.

Biomarkers, Tumor↗
PubMed1996

Using FIGO histologic grade to determine when to perform lymphadenectomies in endometrioid adenocarcinoma of the endometrium.

PURPOSE: Controversy remains as to whether selective pelvic and periaortic lymphadenectomies should be performed in low grade (grade 1 or 2) endometrioid endometrial cancer. The authors reviewed their experience over the last three years in their population of endometrioid adenocarcinomas of the endometrium to see if lymphadenectomies were necessary in low grade malignancies. METHODS: The records of all patients with endometrioid adenocarcinoma of the endometrium undergoing primary surgery by the gynecologic oncology service between November 1, 1991, and August 31, 1994, were analyzed for age, FIGO stage, grade, histologic type, lymphovascular space invasion, peritoneal cytology, and time to recurrence. RESULTS: Sixty-five patients with endometrioid adenocarcinoma of the endometrium were found. Twenty-five had grade I disease, 31, grade 2 disease, and 9, grade 3. Forty-seven patients had stage I disease, 5 stage II disease, 12 stage III disease and 1, stage IV disease. No patient with grade 1 disease had positive lymph nodes on examination. Six with grade 2 (19.4%) and two (22.2%) with grade 3 disease had positive lymph nodes. The percentage of patients with positive lymph nodes was not significantly different between those with grade 2 and 3 disease (p = 0.86) but was significantly different between grade 2 or 3 and grade 1 (p = 0.021) (p = 0.017). CONCLUSION: Pelvic and periaortic lymphadenectomies should be performed as part of standard surgical therapy in patients with FIGO grade 2 endometrioid adenocarcinomas of the endometrium. The decision as to whether to perform lymphadenectomies in grade 1 tumors must be left to the discretion of the surgeon since a chance exists that a higher grade or more deeply invasive tumor may be found on final pathological diagnosis.

Adenocarcinoma↗
PubMed1995

Immunohistochemical assessment of tumor proliferation and volume of embryonal carcinoma identify patients with clinical stage A nonseminomatous testicular germ cell tumor at low risk for occult metastasis.

BACKGROUND: Thirty percent of patients with clinical Stage A nonseminomatous testicular germ cell tumor (NSGCT) are incorrectly clinically staged. In a previous retrospective study at Indiana University, the combination of tumor proliferation rates by flow cytometry and histopathologic evaluation defined risk groups for occult metastatic disease in these patients with clinical Stage A NSGCT: A new immunohistochemical proliferation marker (MIB-1) was therefore used to assess growth fraction in combination with histopathology in an effort to predict pathologic stage in patients with clinical Stage A NSGCT: METHODS: Primary orchiectomy specimens from 90 consecutive patients with clinical Stage A NSGCT (January 1992-November 1993) who underwent retroperitoneal lymph node dissection at Indiana University were histopathologically evaluated. Formalin fixed, paraffin embedded tissue sections were immunohistochemically stained using a monoclonal antibody against the nuclear proliferation-associated antigen Ki-67 (MIB-1). Satisfactory staining was obtained by using an antigen retrieval method based on microwave oven heating of paraffin sections. RESULTS: MIB-1 immunohistochemical staining showed significant differences in mean values between 65 patients (66.1%) with pathologic Stage A NSGCT and 25 (80.4%) patients with pathologic Stage B NSGCT (P = 0.0032). The negative predictive value for patients with pathologic Stage A disease was 87% using a cut-off of 80% or less MIB-1 positively stained cells. A combined approach, using the absolute volume of embryonal carcinoma per patient (< 2 ml) and MIB-1 immunostaining (< or = 80%) was able to define a group of 30% of all patients who were at extremely low risk for occult metastatic disease. CONCLUSIONS: MIB-1 immunostaining in combination with histopathology aided in defining a low risk group patients with clinical Stage A NSGCT but failed to identify patients at high risk for metastasis. The risk factors need to be tested in a prospective clinical trial to determine if they are potentially useful in assigning therapy to individual patients.

Antigens, Neoplasm↗
PubMed1995

Estrogen and progesterone receptors in malignant mixed mesodermal tumors of the ovary.

Malignant mixed mesodermal tumors of the ovary occur in less than 1% of cases of ovarian cancer. They have a dismal prognosis and the most effective type of therapy is still not known. All cases of malignant mixed mesodermal tumor of the ovary between January 1, 1985 and May 1, 1994 operated on by the gynecologic oncology service are the subject of this report. Data were obtained from the hospital and office records of the patients. Nine patients who had their primary surgery by the gynecologic oncology service were found to have the diagnosis of malignant mixed mesodermal tumor of the ovary. Homologous tumors were found in five patients and heterologous tumors in four. Homologous tumors (mean survival 15.2 months) showed a better survival than heterologous tumors (mean survival 6.5 months; P = 0.001). An elevated estrogen receptor status was shown to correspond to longer survival (P < 0.0001). Six specimens were considered to be estrogen receptor positive and three were receptor negative. The mean survival in those patients who had a positive estrogen receptor status, 13.7 months, with a median of 7.5 months was significantly higher than those who were not positive, 6.7 months (P = 0.019) with a median of 6.25 months. All specimens were progesterone receptor negative. Malignant mixed mesodermal tumors of the ovary have a dismal prognosis, no effective therapy, and controversial prognostic indicators. Increasing estrogen receptor status appeared to correlate with longer mean survival. Larger, multi-institutional studies need to be done to determine the overall significance of these findings.

Female↗
PubMed1995

Patterns of perceptual asymmetry in depression and anxiety: implications for neuropsychological models of emotion and psychopathology.

More than 1,000 university undergraduates were simultaneously classified as either high or low depressed and high or low anxious and given a face-processing task that typically elicits a left hemispatial bias. Depression and anxiety were associated with opposing biases in perceptual asymmetry scores. In particular, high-depressed students had smaller left hemispatial biases than low-depressed students, whereas high-anxious students had larger left hemispatial biases than low-anxious students. The results suggest that depression and anxiety may be associated with different patterns of asymmetric hemispheric function. Because the rate of comorbidity of depression and anxiety in the population is high, these findings confirm the importance of separating anxiety and depression when examining the relationship among patterns of brain activity, emotion, and psychopathology.

Anxiety Disorders↗
PubMed1995

Ethnicity and gender in scales of psychosis proneness and mood disorders.

Data for Caucasian, African American, Asian American, and Latino college-student samples were compared for several popular self-report scales of psychopathology. Significant group differences were obtained for all scales, with the Caucasian sample consistently having the lowest means. Some gender effects and interactions with ethnic group were also observed. The authors discuss implications of these findings for use of these scales, including implications for use of Caucasian norms with other ethnic samples.

Adult↗
PubMed1995

Prognostic significance of immunohistochemical proliferation markers (Ki-67/MIB-1 and proliferation-associated nuclear antigen), p53 protein accumulation, and neovascularization in clinical stage A nonseminomatous testicular germ cell tumors.

Histopathologic features alone fail to reliably stratify patients with clinical Stage A nonseminomatous germ cell tumors of the testis into groups with high and low risk for occult metastatic disease. Previous flow cytometric studies at Indiana University demonstrated a significant correlation between high proliferative activity and metastatic disease. The current study evaluated the prognostic significance of immunohistochemical markers related to tumor proliferation and aggressiveness in a consecutive series of clinical Stage A nonseminomatous germ cell tumors patients who underwent retroperitoneal lymph node dissection. Archival material of the orchiectomy specimens of 62 patients (45 pathologic Stage A, 17 with metastatic disease) was reviewed and immunohistochemically stained for Ki-67 antigen (MIB-1), proliferation-associated nuclear antigen (PC10), p53 protein (Pab1801), and Factor-VIII-related antigen (neovascularization). Staining with MIB-1 was significantly higher in the metastatic group (mean 80.2%, standard deviation [SD] 15.5) than in pathologic Stage A cases (66.3%, SD 27.9; P = 0.0032) and was predictive of metastatic status with a sensitivity of 82% and specificity of 69%. In this study, no patient with a MIB-1 value less than 52% had metastases. Proliferation-associated nuclear antigen and p53 staining correlated with MIB-1 values (R = 0.63 and 0.55, respectively) but did not correlate with metastatic status. Tumor angiogenesis was also not predictive of metastatic status. Assessment of proliferation rates using MIB-1 antibody in clinical Stage A nonseminomatous germ-cell-tumor patients may prove helpful in predicting metastatic status.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗
PubMed1995

[New parameters for prediction of pathological stage in clinical stage I non-seminomatous testicular tumors].

Traditional histopathological risk factors have failed to predict pathological stage accurately in clinical stage I nonseminomatous testicular germ cell tumours. Histopathology, flow cytometry, cytophotometry, and immunohistochemical staining techniques were used in an effort to define high- and low-risk groups for occult metastasis in a consecutive series of 105 patients who underwent retroperitoneal lymph node dissection. After multiple logistic regression analysis, the proliferative S + G2M cell cycle fraction of the aneuploid tumour stemline was the most highly predictive parameter of pathological stage (P = 0.0004). Using a cut-off of 41%, pathological stage II patients were predicted with a sensitivity of 71%. There were 61 patients with S + G2M values below 41%, and 43 of them had pathological stage I disease (negative predictive value 87%). A low volume of embryonal carcinoma was predominant in low-risk patients, and MIB-1 immunohistochemical staining identified a subgroup of 23% of patients with pathological stage I disease and at extremely low risk of metastatic disease. Assessment of tumour cell proliferation does not allow accurate classification of high-risk patients at a level that is adequate for clinical application. Patients who are at low risk of metastasis, however, can be identified by flow cytometry, immunohistochemical proliferation markers and volume of embryonal carcinoma with 90% certainty. These parameters deserve further study, since identification of a subgroup of patients at extremely low risk of metastasis could potentially reduce the overall morbidity in the management of clinical stage I nonseminomatous testis cancer.

Animals↗
PubMed1995

Change in MIB-1 staining between primary and recurrent epithelial ovarian cancer.

PURPOSE: In recent articles, MIB-1 staining has been shown to relate to length of survival of patients with epithelial ovarian malignancies. We report a case showing the difference in MIB-1 between the primary and recurrent tumor. CASE REPORT: A 63 year old female had a total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and paraaortic lymphadenectomy, partial omentectomy, and a staging procedure which achieved optimal debulking of a clear cell adenocarcinoma of the ovary. Final pathology revealed Stage IIIc disease because of one positive left iliac node. All other specimens except for the ovaries were negative for malignancy. The proliferation index of the tumor based on MIB-1 monoclonal antibody staining was 4.10%. The patient then was treated with 6 courses of carboplatin and cyclophosphamide. After a microscopically positive second look laparotomy, the patient received 4800 cGy of external beam radiation to the pelvic and paraaortic lymph node bearing areas. Fifteen months after the original diagnosis, a suspicious vaginal mass was biopsied and found to be recurrent clear cell adenocarcinoma consistent with an ovarian primary. MIB-1 monoclonal antibody staining of the recurrent cancer gave a proliferation index of 38.73%. The patients is still alive with a CA-125 which has plateaued between 60 U/ml and 70 U/ml, fourteen months after recurrence. CONCLUSION: The proliferation index by MIB-1 staining may be affected by treatment for ovarian epithelial malignancies.

Adenocarcinoma, Clear Cell↗
PubMed1994

Does preoperative chemotherapy for hepatic tumors have an adverse effect on hepatic proliferation after delayed liver resection?

The authors evaluate the effect of preoperative cisplatin and Adriamycin on hepatic proliferation after delayed partial hepatectomy. Sprague-Dawley rats were placed into five experimental groups. Group I received 0.9% saline intraperitoneally (IP). Group II received 2 mg/kg of cisplatin IP. Group III received 4 mg/kg of cisplatin IP. Group IV received 6 mg/kg of Adriamycin intravenously. Group V received 0.9% saline IP. Groups I through IV underwent 70% partial hepatectomy 2 and 10 days after chemotherapy. They were killed 24 hours later, and analyses were performed. Group V animals underwent celiotomy and were killed. Hepatic proliferation was evaluated by tritiated thymidine (3H-TdR) incorporation into DNA, quantitative image analysis (QIA), and proliferating cell nuclear antigen immunostained hepatic nuclei (PCNA). 3H-TdR incorporation values in animals treated 2 days before partial hepatectomy in treatment groups II through IV were similar to those of the hepatectomized controls. Although among the animals treated 10 days before partial hepatectomy there was inhibition of 3H-TdR DNA incorporation in the Adriamycin group, no significant differences were noted between all treatment groups. QIA of the S-phase nuclei (an indicator of proliferation) indicated that the animals treated with 2 mg/kg of cisplatin had significantly more nuclei than those treated with Adriamycin. PCNA labeling showed a decrease in proliferating nuclei in all treatment groups compared with the control hepatectomized animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Season, gender, and P300.

Light therapy in patients with seasonal affective disorder has been reported to enhance visual P300 amplitude. This findings raises the possibility that variations in P300 occur naturally in nonpatients as a function of seasonal variation in sunlight. In the present investigation, P300 was studied in a sample of psychiatrically screened normal subjects who were tested at different times of the year. P300 was larger in women than men and varied in relation to season. This pattern is relevant to studies in which subjects are tested under varying sunlight conditions, such as different seasons. In addition, variations in P300 in normal subjects may be relevant to an understanding of the effectiveness of light therapy for patients with seasonal affective disorder.

Adult↗
PubMed1994

A dual-task analysis of resource allocation in dysthymia and anhedonia.

Research has shown dysthymic individuals to be hyporesponsive at various stages of information processing, yet it is not clear whether dysthymics are deficient in the amount of available attentional resources for information processing or, instead, in the allocation of those resources. To distinguish between these possibilities, the authors compared dysthymics to anhedonic and normal control Ss during the performance of memory tasks, under conditions of varying task priority and difficulty. Although there were no performance differences, dysthymics and anhedonics exhibited a consistently smaller P300 component of the event-related potential. Furthermore, P300 results indicated that dysthymics and anhedonics responded differently from controls to variations in task demands. Thus, although evidence was obtained for group differences in both resource capacity and resource allocation strategy, the overall pattern of results is interpreted as favoring the latter.

Attention↗