MHC status of primary human colorectal carcinoma: biological significance and implications for host immune recognition.
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Biomedical subjects
Publications and source records attributed to M Moore.
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The information age demands that health sciences librarians take active roles in the educational process. Librarians have traditionally taught users how to access information. Now, with the proliferation of information, librarians must accept new roles and teach the user efficient techniques for evaluating and processing information as well. Innovative roles for librarians at Texas Tech University Health Sciences Center include teaching users to use technology for information management, to appraise literature critically for quality, and to develop skills for lifelong learning. This paper reviews the history of educational activities in health sciences libraries and describes the teaching programs at Texas Tech.
The incorporation of iododeoxyuridine (IdUrd) into Chinese hamster cells was examined as a possible radiosensitizer for fission spectrum neutrons. Dose-response curves comparing both X rays and neutrons in the same cell line with the same IdUrd replacement showed a similar radiation enhancement for IdUrd incorporation. Enhancement ratios at the 1% survival level were 1.8 for X rays and 1.5 for fission spectrum neutrons. While the mechanism of this enhancement in the response for fission neutron radiation is unclear, these positive data should support further exploration to determine if halogenated pyrimidine incorporation results in sensitization for neutron energies employed in therapy.
The specific and non-specific nature of autotumor cytotoxicity induced in autologous mixed lymphocyte-tumor culture (AMLTC) and autologous mixed lymphocyte culture (AMLC) was studied in patients with carcinomatous pleural effusions. Small- and medium-sized blood lymphocytes that were isolated by centrifugation on discontinuous Percoll gradients did not lyse autologous, freshly isolated effusion tumor cells. In vitro activation of the small lymphocytes, but not of the medium lymphocytes, with autologous tumor cells generated cytotoxic potential restricted to autologous tumor. When stimulated with autologous non-malignant non-T cells, the medium lymphocytes, but not small lymphocytes, were triggered to cytotoxicity that acted not only on autologous tumor cells but also on allogeneic tumor cells, T blasts, and tumor cell lines. Experiments using monoclonal antibodies (MAb) and complement (C') showed that both types of killer cells were CD2+ CD3+ CD16- T cells. Autotumor cytotoxicity developed in AMLTC was mediated by the CD4- CD8+ T cell subset in 6 of 9 cases and the CD4+ CD8- subset in the other 3 cases. In contrast, cytotoxicity induced in AMLC was exerted exclusively by the CD8+ subset. The enrichment of blasts from cultured T cells on discontinuous density gradients enhanced autotumor killing activity, with no reactivity recorded for blast-depleted, resting T cells. Addition of mitomycin-C-treated large granular lymphocytes (LGL) to AMLTC abolished the induction of autotumor killer cells, whereas non-specific killer cells were generated in AMLC irrespective of the presence of LGL. These results indicate that stimulation of autoreactive T cells in AMLTC and in AMLC could induce 2 distinct types of autotumor killer cells.
A consecutive series of 123 colorectal cancers, prospectively followed for 3 years, was studied to determine if the prognostic significance of DNA ploidy related to: (a) thresholds used to define DNA aneuploidy, or (b) aneuploid sub-groups defined by DNA index (DI) and peak size. Aneuploidy was defined using 3 methods depending on the minimum proportion of nuclei considered to constitute an aneuploid peak; type 1, 5%; type 2, 10%; type 3, 10% if DI is 1.1-1.8, but 15% if DI is 1.9-2.1. DNA aneuploidy rates were type 1, 75%; type 2, 67%; type 3, 58%. The significance of clinical and pathological correlations varied with the use of different methods. All were associated with a significant DNA diploid survival advantage which was strongest for type 3 (p = 0.006). DI was unrelated to survival irrespective of the presence or absence of an associated S/G2; 33% with a DI of 1.1-1.8 and 35% with a DI of 1.9-2.1 survived. Prognosis was inversely proportional to aneuploid peak size, 48% with small peaks (less than 20%), 30% with intermediate peaks (greater than 20% less than 40%), but none with large peaks (greater than 40%) survived (p = 0.03). We conclude that: (a) thresholds used to define DNA aneuploidy affect the prognostic significance of DNA ploidy; (b) survival is independent of the DI of aneuploid peaks; and (c) measurement of aneuploid peak size refines the prognostic value of DNA ploidy.
The influence of lead selection on QT estimation in the 12-lead electrocardiogram was assessed in 63 patients (21 control subjects, 21 with anterior myocardial infarction, 21 with inferior myocardial infarction). QT estimates varied between leads. The variation was greater in patients with myocardial infarction than in control subjects (mean dispersion of QT: control subjects, 48 +/- 18 ms [+/- standard deviation]; anterior myocardial infarction, 70 +/- 30 ms; inferior myocardial infarction, 73 +/-32 ms). The maximum QT in any lead (QTmax) was determined and the deviation of each lead from this maximum value calculated. In all 3 groups, anteroseptal leads (V2 or V3) provided the closest approximation to QTmax. Interlead variability was found to be mainly due to variation in timing of the end of the T wave, rather than the onset of the QRS complex. The variability due to leads was considerably greater than the variability due to cycles, observers or measurement error. Implementation of a variety of current lead selection practices resulted in widely divergent estimates of QT interval. It is concluded that there is a need for standardization of lead selection practice for QT measurement. If measurements are confined to one or a few leads, anteroseptal leads provide the closest approximation to QTmax.
A prospective study of prognostic factors has been carried out in a group of 123 consecutive patients with colorectal cancer. The fate of all patients is known at 3 years after operation. Clinical and pathological data were recorded at the time of presentation and operation, and the patients have been subject to regular postoperative review. DNA ploidy status was determined by flow cytometry. In all, 39 (33 per cent) patients had DNA diploid tumours and 80 (67 per cent) patients had DNA aneuploid tumours. In four cases, tumour material was not obtained. The patients with DNA aneuploid tumours had a worse prognosis than those with DNA diploid tumours, but this was only seen in those patients classified as Dukes' B. In a Cox's regression analysis, the surgeon's assessment of operability was the strongest predictor of survival, followed by the pathological classification and the patient's age. After these factors had been considered, the DNA ploidy status conferred no independent survival value.
An optical system for measuring changes in cell length during unloaded contractions of cardiac myocytes is described. A one-dimensional video "image" of a cell is obtained every 4 ms with a linear photodiode array, which is aligned with the longitudinal axis of the cell. The circuit used to process the image from the photodiode array has a variety of features to aid in the accurate determination of the distance between the ends of the cell, i.e. the cell length. First, the video image of the cell is divided into two "windows", one encompassing the "front" edge of the cell, the other encompassing the "rear" edge. Other cells or debris beyond the cell edges are excluded. Changes in the general light level, for example as a result of debris floating above the cell, have little effect because within the windows the "background light level" is subtracted from the signals before they are processed further. To detect the cell edges, the system determines when the signals within the windows exceed (front edge) or drop below (rear edge) chosen thresholds, which are different for the front and rear edges. The system has "memory" and it identifies the rear edge of the cell as the last time the signal falls below the threshold; because of this "bright spots" within the cell are not mistaken for the end of the cell. The system has "hysteresis", which enables it to ignore small fluctuations in brightness around the threshold. The system is easy to use, accurate, readily calibrated, and it has good spatial and time resolution (about 0.25 micron and 4 ms respectively).
In vivo sensitivity of Plasmodium falciparum to chloroquine was evaluated in 4 of 9 regions of Zaire in 1985 to develop a national strategy for treatment of malaria. Children less than 5 years of age were treated with either a single dose of chloroquine base, 10 mg/kg, or a dose of 25 mg/kg given over 3 d. A modified 7-day World Health Organization in vivo test was used with follow-up 2, 3 and 7 d after the start of treatment. 339 children were studied. In Bwamanda 92% of children were aparasitaemic 7 days after chloroquine, 10 mg/kg, but in Kinshasa only 44% were free of parasites after 25 mg/kg chloroquine. The mean drop in parasite density among those who did not clear parasites by day 7 was greater than 98% of the initial value. Although the parasite density decreased markedly, the failure of most subjects to become aparasitaemic indicated a marked decrease in parasite sensitivity since 1983. Only one child of 51 who were initially febrile remained febrile, although 14 (28%) of these had resistant parasites. The decrease in parasitaemia and temperature, even among children with resistant strains, led the Ministry of Health to recommend 25 mg/kg chloroquine as first line treatment for fever/malaria in their national malaria control plan. The plan includes drug sensitivity surveillance and a referral system for patients who do not respond to chloroquine treatment.
The presence of a number of regulatory peptides (bombesin, gastrin, glucagon, somatostatin, calcitonin and ACTH) was compared in 30 typical carcinoid tumours and 27 well differentiated neuroendocrine carcinomas (atypical carcinoids) using conventional immunocytochemistry. Strong immunostaining for one or more peptide was observed in 97% of the typical carcinoids (29/30) whereas only 67% of the neuroendocrine carcinomas showed immunoreactivity. The peptide most frequently detected in typical carcinoids was bombesin (67%), while gastrin was more common in neuroendocrine carcinomas (44%). Immunoreactivity for more than one peptide was present in 33 tumours and in three cases, six different peptides were detected. The study shows that immunoreactivity to various peptides is more common in typical carcinoids than well differentiated neuroendocrine carcinomas. The significance of these findings is discussed.
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In five maternity centres in urban and rural Zaire we evaluated the maternal prevalence of Plasmodium falciparum parasitaemia and recorded fever, the frequency of abortions and stillbirths, newborn birth weights and the feasibility of delivering antimalarial chemoprophylaxis. Women in their first and second pregnancy, compared to others (greater than or equal to third pregnancies), had a higher frequency of parasitaemia (38 v. 15%, respectively, P less than 0.001), higher parasite densities (geometric mean densities 927 per mm3 v. 277 per mm3, respectively, P = 0.01), higher rates of stillbirths and low birth weight babies (24% v. 6.4%, P less than 0.001). On average, pregnant women first attended prenatal clinics in the sixth to seventh month of gestation and made three to four visits before delivery. In these areas of Zaire, antimalarial interventions during pregnancy would have the largest impact if they were targeted to women in their first and second pregnancy. In the study areas, maternal attitudes and prenatal care-seeking behaviours do not appear to be barriers to providing an antimalarial intervention.
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To assess the clinical value of two comparatively new properties (DNA content and MHC class II antigen expression (HLA-DR, DP, DQ) of melanoma cells) which have been independently reported to reflect the outlook for patients with malignant melanoma, we investigated retrospectively 50 stage I nodular melanomas in two comparably homogeneous groups of 23 and 27 patients, the course of whose disease differed at five years. Flow cytometry and immunohistology were used on paraffin wax embedded archival material for the analysis of DNA ploidy and detection of class II antigens, respectively. A close association was found between class II antigen expression, detected by monoclonal antibody CR3/43 (antimonomorphic DR, DP, DQ) present in 23 of 50 (46%) melanomas and unfavourable clinical course (p less than 0.005, by log rank test), but no such association was found for DNA ploidy. It is suggested that immunohistology for MHC class II antigen expression may help to predict the behaviour of nodular melanomas whereas the prognostic value of DNA ploidy is more limited. The finding that class II positive cells are found predominantly in melanomas with a substantially increased risk of metastases has implications both for concepts of tumour heterogeneity and host immunity.
Fifty three bronchopulmonary carcinoid tumours were studied to assess the significance of DNA ploidy, determined by flow cytometry of paraffin embedded tissue. Twenty eight were typical carcinoid tumours and 25 well differentiated neuroendocrine carcinomas. Twenty seven were DNA diploid and 26 DNA aneuploid. DNA aneuploidy was significantly associated with histological features of increased malignant potential. Survival data were available for 43 patients. Of the 19 with DNA diploid tumours, 16 survived five years, compared with 14 of 24 with DNA aneuploid tumours--the difference being at the borderline of statistical significance. In a Cox multivariate regression analysis with other histological variables, DNA ploidy did not confer independent prognostic information. It is concluded that, although DNA aneuploidy as determined by flow cytometry is an indicator of increased malignant potential in bronchopulmonary carcinoid tumours, it does not provide clinically useful information additional to the results of routine histological examination.
We studied breathing and behavioral response to increased arterial CO2 (PaCO2) in 12 fetal sheep between 130 and 145 days of gestation. Of these 12 fetuses, 10 had an increase in PaCO2 through maternal rebreathing of CO2; in the other 2 fetuses CO2 was increased via an endotracheal tube and application of continuous distending airway pressure. We used our window technique to observe and videotape fetal behavior. The experiments consisted of recording breathing activity and behavior during resting conditions (1 low- and high-voltage ECoG cycle) and during administration of CO2. We measured electrocortical activity (ECoG), eye movements (EOG), electromyography of the diaphragm (EMGdi) and neck muscles, tracheal (Ptr), amniotic, and carotid arterial pressures. Administration of CO2 by the rebreathing technique produced an increase in the amplitude of breathing activity as reflected by an increase in Ptr from 5.0 +/- 0.6 to 12 +/- 1.9 mmHg (P less than 0.01) and an increase in SEMGdi from 32 +/- 4 to 77 +/- 8% max (P less than 0.001). Frequency increased due to a decrease in inspiratory (TI) and expiratory duration. Ptr/TI increased from 11.0 +/- 2.0 to 37.4 +/- 9.0 mmHg/s (P less than 0.05) and SEMGdi/TI increased from 67 +/- 7 to 221 +/- 28% max/s (P less than 0.001). Although the response was at times prolonged into the transitional high-voltage zone, it did not persist during established high-voltage ECoG.(ABSTRACT TRUNCATED AT 250 WORDS)
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