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Biomedical subjects

B H Smith

Publications and source records attributed to B H Smith.

At least 109 records · Page 6Linked to original sources
PubMed1984

[Immunocytochemical localization of factor VIII-related antigen in blood vessels of the human central nervous system].

Using both immunohistochemical and immunoelectron microscopic techniques with periodatelysine-paraformaldehyde (PLP) fixation, we have studied the distribution of Factor VIII-related antigen (F VIII R: Ag) in 14 cases of human central nervous system (CNS) tumors and 1 sample of non-tumor brain tissue. F VIII R: Ag was localized to the vascular lumen, to the intercellular spaces between endothelial cells (apparently without tight junctions), and to the endothelial cell basement membrane. In the cytoplasm, F VIII R: Ag was found in the endoplasmic reticulum, perinuclear space, and intracytoplasmic vacuoles and vesicles only. Characteristic of malignant tumors (6 out of 7) was strongly-positive dilated endoplasmic reticulum, whereas only 1 of 5 benign tumors showed such staining. This appears to reflect increased F VIII R: Ag synthesis in the malignant vessels. The non-tumor brain tissue showed normal capillary structure and very little F VIII R: Ag immunoreactivity. Six of 12 tumors and the non-tumor brain showed perinuclear F VIII R: Ag. Although the basement membranes were more irregular in the malignant tumors, staining was not grossly different from that of the more benign lesions. The finding of both ad-and ablumial vesicles containing F VIII R: Ag suggests that endocytosis, transcellular transport, and/or exocytosis, as well as F VIII R: Ag synthesis, occurs in the tumor endothelial cells. The relationship of these F VIII R: Ag abnormalities to the hypercoagulable state seen in some malignant brain tumor patients remains to be clarified.

Adenocarcinoma↗
PubMed1984

In vitro studies on the cell-mediated immune response to human brain tumors. II. Leukocyte-induced coats of glycosaminoglycan increase the resistance of glioma cells to cellular immune attack.

We have examined the ability of cultured human glioma cells to elicit allogeneic cytolytic lymphocyte responses in vitro in order to delineate properties of glioma cells that may contribute to their ability to escape cellular immune attack. When glioma cells were cultured together with allogeneic peripheral blood mononuclear cells (PBMC) in mixed lymphocyte-tumor cultures (MLTC), it was observed that cells from eight of 12 glioma lines were surrounded by clear pericellular "halos," which appeared to impede contact between PBMC and the glioma cells. Enzymatic, histochemical, and immunochemical studies indicated that these halos represented glycosaminoglycan (GAG) coats that contained hyaluronic acid (HA) as a major constituent. Electron microscopic studies demonstrated the presence of many thin microvillous processes spanning the width of the halos. The presence of GAG coats around glioma cells in MLTC reduced the generation of cytolytic T lymphocytes specific for antigens on the glioma cells. Likewise, these cell coats decreased the lysis of glioma cells by cytolytic lymphocytes, once generated. The production of thick coats of GAG by glioma cells was induced by interaction of glioma cells with a nondialyzable factor produced by PBMC in culture. This factor did not cause glioma cells to release increased amounts of HA into the medium, but rather increased the production of HA that remained associated with the glioma cell surface. The formation of thick, protective GAG coats by glioma cells as a result of their interaction with the PBMC-derived factor constitutes a nonspecific suppressor mechanism that may contribute to the ability of this class of human solid tumors to evade cellular immune attack.

Brain Neoplasms↗
PubMed1983

Autologous serologic responses in glioma patients. Correlation with tumor grade and survival.

The serologic responses of 42 patients with gliomas have been evaluated in a quantitative microcytotoxicity assay utilizing autologous cultured glioma cells. Forty-five percent of patients had detectable cytotoxic antibody apparently directed to their own cultured cells. When tumor grade was correlated with immune response, 15/20 patients with Grade I, II and III astrocytomas had antigens detectable in autologous sera whereas only 5/22 patients with Grade IV astrocytomas had such responses. None of the autologous fibroblasts from the 15 patients with paired gliomas and fibroblast lines had membrane antigens detectable using autologous sera and fibroblast absorption did not reduce antiglioma activity. Thus, the cytotoxicity observed in this assay appears to be restricted to tumor cells, suggesting reactivity against tumor-associated antigen. In addition, it appears that these immune responses are highly correlated with survival in primary malignant brain tumor patients.

Antibodies, Neoplasm↗
PubMed1983

Lymphoid cell-glioma cell interaction enhances cell coat production by human gliomas: novel suppressor mechanism.

Certain human glioma lines produce mucopolysaccharide coats that impair the generation of cytolytic lymphocytes in response to these lines in vitro. Coat production is substantially enhanced by the interaction of glioma cells with a macromolecular factor released by human peripheral blood mononuclear cells in culture. This interaction thus constitutes an unusual mechanism by which inflammatory cells may nonspecifically suppress the cellular immune response to at least one class of solid tumors in humans.

Animals↗
PubMed1983

Membrane and cytoplasmic changes in 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU)-sensitive and resistant human malignant glioma-derived cell lines.

Human glioma-derived cell lines previously determined by a microtiter chemotherapy assay to be either 'sensitive' or 'resistant' to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) were treated with BCNU (1-80 micrograms/ml) and observed using microcinematography, scanning electron microscopy, and transmission electron microscopy. Striking bleb formation and cell retraction were observed to occur in a dose-dependent relationship within minutes in the cells known to be BCNU-sensitive. At 15 micrograms/ml, 69% of cells showed blebs by 30 min, 87% by 90 min, and 100% by 4 hr. This activity was not seen in BCNU-resistant cells. These morphological changes occur at a time too early to be accounted for by the known BCNU mechanism of DNA alkylation and cross-link formation and suggest that cytoplasmic and/or membrane events may be significant initial events in the cytotoxic actions of BCNU.

Adult↗
PubMed1983

Flowcytometric and cytogenetic analysis of human cultured cell lines derived from high- and low-grade astrocytomas.

Five human cell lines cultured from high- and low-grade astrocytomas in cerebral hemisphere have been analyzed for DNA and protein distribution by flowcytometric (FCM) and correlated with cytogenetic profiles. Simultaneous calibration with chicken erythrocytes as a co-running standard provided an estimate of chromosomal number of predominate stem cells of each cell line by the ratio of the DNA content of the major peak (G1) to that of chicken erythrocyte (T/E ratio) of FCM. Various lines had different distributions of chromosomal number, ranging from near diploid to tetraploid. Each line had a stem-cell population and chromosomal markers indicative of clonal selection, but no common marker specific to astrocytomas. The histogram of DNA distribution obtained by FCM correlated well with the chromosomal distribution by cytogenetic analysis. In addition, simultaneous measurement of protein and DNA content in multidimensional FCM demonstrated a sigmoid configuration of the profiles, which indicated a gradual increase of protein content associated with an increase of chromosomal number or with progression of cell cycle. To avoid confusion of a bimodal chromosomal distribution with the G2/M phase of the cell cycle, and to determine chromosomal numbers associated with a DNA histogram, simultaneous cytogenetic and FCM study are required. More rapid than cytogenetic analysis, the T/E ratio allows estimation of chromosomal number of the stem-cell population associated with DNA histograms of cultured glioma-derived cell lines.

Astrocytoma↗
PubMed1983

Radiosensitization of hematopoietic precursor cells (CFUc) in glioblastoma patients receiving intermittent intravenous infusions of bromodeoxyuridine (BUdR).

The potential use of bromodeoxyuridine (BUdR) as a radiosensitizer given by an intermittent intravenous route is being studied in a Phase I/II trial at the National Cancer Institute. In order to assess the extent of radiosensitization, we have studied the radiation response of human bone marrow cells CFUc taken from 6 patients prior to and after a 14-day infusion of BUdR. Varying concentrations (1000-1500 mg) of BUdR were infused for 12 hours every 24 hours for up to 14 consecutive days. Cell survival was determined by colony formation of CFUc in soft agar suspension. X ray survival curves were generated over a dose range of 0-300 rad and the slopes of the survival curves (DO) before and after BUdR infusion were compared. Radiation enhancement ratios (ER) (DO pre-BUdR/DO post-BUdR) ranged from 1.0-2.2 and appeared to be BUdR dose dependent. Above 650 mg/m2, the radiation ER was greater than or equal to 1.5. Dose dependent systemic toxicity to bone marrow and skin was also observed with intermittent intravenous infusions of BUdR. From our study, it appears that an intravenous dose of less than 700 mg/m2/12 hours is well tolerated and may result in radiosensitization of CFUc in man.

Adult↗
PubMed1983

Recognition of female kin by male bees through olfactory signals.

After males of Lasioglossum zephyrum (Hymenoptera: Halictidae) have first been exposed to a conspecific female, the attractiveness of a second female diminishes with increasing genealogical relationship between the two females. The most parsimonious explanation for this is a polygenically controlled female sex pheromone. Nonrandom mating preferences may markedly affect gene flow within and between natural populations. Polygenically controlled sex pheromones probably also enhance kin recognition among females and, thus, influence the evolution of eusocial behavior in bees and wasps.

Journal Article↗
PubMed1983

Metabolic imaging of the brain stem and spinal cord: studies with positron emission tomography using 18F-2-deoxyglucose in normal and pathological cases.

A new high resolution positron emission scanner (Neuro-PET) has made possible clear visualization and quantitation of glucose metabolism in the brain stem and upper cervical cord (above C4) using 18F-2-deoxyglucose. The following mean measurements of the glucose utilization rate are based on studies of 34 normal volunteers and patients with no apparent pathology in the brain stem or cord: 5.0 +/- 1.0 (SD) mg Glu/100 g/min for the mesencephalon-upper pons, 3.2 +/- 1.0 for the pons-medulla, and 1.7 +/- 0.6 for the upper cervical cord. (The first value also includes studies done with the ECAT-II scanner.) Resolution of white-gray matter within these structures was not possible. Whenever possible, a correlation was made with autoradiographic data in monkeys, and good agreement was found. The glucose utilization in cases showing brain stem and cord pathology was altered, with marked elevation (as high as 8.2 mg/100 g/min) in cases of high-grade gliomas, and reduction in cases of low-grade gliomas and one pontine hematoma.

Adult↗
PubMed1983

Mitochondrial toxicity of 2,5-diaziridinyl-3,6-bis-(carboethoxyamino)-1,4-benzoquinone.

2,5-Diaziridinyl-3,6-bis-(carboethoxyamino)-1,4-benzoquinone (AZQ) is an antitumor agent characterized by lipid solubility and the ability to penetrate the central nervous system. Two human glioma-derived cell lines, SNB-1 and SNB-2, proved by microcytotoxicity assay to be sensitive to AZQ, were examined with transmission electron microscopy for morphologic changes induced by this drug. AZQ was used in two ways: a) dissolved with dimethylacetamide (aqueous) at concentrations of 25 and 50 micrograms/ml and b) solid (surface plated) at 3.1 and 6.2 micrograms/mm2. A time study from 30 minutes to 48 hours was performed. Selective mitochondrial destruction was noted after 8 hours of exposure to AZQ. After 12 hours, condensation of chromatin along the periphery of the nucleus and dilation of endoplasmic reticulum were two other cellular reactions observed. Thus in addition to the known alkylating activity of AZQ, it has significant mitochondrial toxicity. This antimitochondrial effect is possibly an important factor in the antiglioma cell cytotoxicity of AZQ.

Antineoplastic Agents↗
PubMed1983

Phase II and pharmacokinetic study of aziridinylbenzoquinone [2,5-diaziridinyl-3,6-bis(carboethoxyamino)-1,4-benzoquinone, diaziquone, NSC 182986] in high-grade gliomas.

2,5-Diaziridinyl-3,6-bis(carboethoxyamino)-1,4-benzoquinone (AZQ; Diaziquone, NSC 182986) is a rationally designed antitumor drug possessing sufficient lipid solubility to allow penetration into the central nervous system. Thirty-one patients with high-grade glioma and progressive disease following radiation, with or without previous chemotherapy, have been treated with 144 cycles of drug, consisting of 20 mg/sq m given as an i.v. infusion on Days 1 and 8 of a 28-day cycle. Responses were measured by serial computer tomography scanning. Of the 28 evaluable patients, 6 (21%) had limited improvement (10 to 40% reduction in tumor size) on computer tomography scan, 10 (36%) had disease stabilization, and 12 (43%) had progressive disease. The drug was well tolerated clinically, with little acute toxicity. The major toxicity was myelosuppression, which appeared cumulative, using this dose regimen. AZQ was measurable in both tumor tissue and tumor cyst fluid in patients on therapy. Plasma samples taken during the period of infusion confirm that 50% or more of the total AZQ exposure occurs during the infusion period. AZQ behaves as intended by design and demonstrates activity in this poor-prognosis group of patients.

Adult↗
PubMed1982

Allometric scaling in the dentition of primates and prediction of body weight from tooth size in fossils.

Tooth size varies exponentially with body weight in primates. Logarithmic transformation of tooth crown area and body weight yields a linear model of slope 0.67 as an isometric (geometric) baseline for study of dental allometry. This model is compared with that predicted by metabolic scaling (slope = 0.75). Tarsius and other insectivores have larger teeth for their body size than generalized primates do and they are not included in this analysis. Among generalized primates, tooth size is highly correlated with body size. Correlations of upper and lower cheek teeth with body size range from 0.90-0.97, depending on tooth position. Central cheek teeth (P44 and M11) have allometric coefficients ranging from 0.57-0.65, falling well below geometric scaling. Anterior and posterior cheek teeth scale at or above metabolic scaling. Considered individually or as a group, upper cheek teeth scale allometrically with lower coefficients than corresponding lower cheek teeth; the reverse is true for incisors. The sum of crown areas for all upper cheek teeth scales significantly below geometric scaling, while the sum of crown areas for all lower cheek teeth approximates geometric scaling. Tooth size can be used to predict the body weight of generalized fossil primates. This is illustrated for Aegyptopithecus and other Eocene, Oligocene, and miocene primates. Regressions based on tooth size in generalized primates yield reasonable estimates of body weight, but much remains to be learned about tooth size and body size scaling in more restricted systematic groups and dietary guilds.

Animals↗
PubMed1982

Problems of sampling and inference in the study of fluctuating dental asymmetry.

Randomly distributed or "fluctuating" dental asymmetry has been accorded evolutionary meaning and interpreted as a result of environmental stress. However, except for congenital malformation syndromes, the determinants of human crown size asymmetry are still equivocal. Both a computer simulated sampling experiment using a combined sample size of N = 3000, and the requirements of adequate statistical power show that sample sizes of several hundred are needed to detect population differences in dental asymmetry. Using the largest available sample of children with defined prenatal stresses, we are unable to find systematic increases in crown size asymmetry. Given sampling limitations and the current inability to link increased human dental asymmetry to defined prenatal stresses, we suggest that fluctuating dental asymmetry is not yet established as a useful and reliable measure of general stress in human populations.

Body Height↗