Search PubMed⌕ Search

Biomedical subjects

G M Hahn

Publications and source records attributed to G M Hahn.

At least 109 records · Page 6Linked to original sources
PubMed1982

Nonspecific stabilization of stress-susceptible proteins by stress-resistant proteins: a model for the biological role of heat shock proteins.

It is demonstrated experimentally that addition of proteins that are themselves resistant to denaturation by heat or ethanol can nonspecifically stabilize other proteins that are ordinarily highly susceptible to inactivation. It is proposed that the diffusion-limited rate with which unfolded protein molecules encounter each other and become irreversibly crosslinked is reduced in the presence of substantial concentrations of an unreactive globular protein. We suggest that one of the functions of heat shock proteins, which are synthesized in large amounts after exposure of cells to increased temperature and other forms of stress, may be to stabilize other proteins kinetically in a similarly nonspecific fashion.

Alkaline Phosphatase↗
PubMed1982

Clinical studies with ultrasound-induced hyperthermia.

Results obtained in clinical studies in which ultrasound was used for hyperthermia induction are reviewed. High intensity ultrasound has certain advantages for the induction of local hyperthermia: Well-collimated beams can be produced, which makes good localization possible; ultrasound can be focused; and absorption in tissue is proportional to frequency, hence the depth of penetration can be controlled. Limitations include the fact that ultrasound is reflected from tissue-air interfaces and thus cannot be used to heat tumors in the lung. Local "hot spots" due to impedance mismatches that result in standing wave patterns may occur near bone. During clinical treatments, this latter problem is frequently associated with a patient's complaint of pain. The temperature generated depends both on ultrasound absorption coefficients, which vary among different tissues, and dissipation of heat, which varies due to local differences in blood flow rates. Thus inhomogeneities of heating in tissue may be observed despite uniform ultrasound fields. Clinical results with ultrasound-induced hyperthermia have been reported by groups at Stanford, M.D. Anderson Hospital, and Massachusetts Institute of Technology-Harvard. Approximately 40-50% of the superficial tumors showed an objective response to ultrasound hyperthermia in the range of 43 degrees -50 degrees C. Responses to heat alone were partial and transitory. Some radiation responses appeared to be improved by concomitant ultrasound hyperthermia.

Adenocarcinoma↗
PubMed1982

Interactions of hyperthermia and drugs: treatments and probes.

At temperatures above 37 degrees C, the abilities of many, but not of all, anticancer drugs to kill cells increases substantially. The increased cytotoxic rate can vary smoothly with temperature (e.g., nitrosoureas or cis-platinum(II) diamminedichloride) or show a marked threshold near 43 degrees C (e.g., adriamycin or bleomycin). Clinically, the increased cell killing rate can be used in the combination of localized hyperthermia and systemic chemotherapy. Drugs can also be useful in the study of cell killing by heat. Aliphatic alcohols which mimic and interact with heat, tend to be localized in lipid-rich regions of the cell, i.e., membranes. Heat modifies the rate at which plant lectins agglutinate cells and also modifies capping rates; most likely, these changes reflected membrane alterations. Because other data strongly imply that proteins are involved in cell death, we think that the first step in hyperthermic killing of cells involves damage to specific membrane-associated proteins.

Alcohols↗
PubMed1981

Temperature-induced homeoviscous adaptation of Chinese hamster ovary cells.

Exponential and plateau phase Chinese hamster ovary cells were maintained for 3 days at 32, 37, 39 or 41 degrees C. The effect of growth temperature on the fluidity and composition of the cellular membranes, and on the ability of the cells to resist a subsequent heat treatment at 43 degrees C, was measured. Cells grown at temperatures above 37 degrees C displayed increased resistance or tolerance to a 43 degree C heat treatment, whereas cells grown at 32 degrees C were sensitized to heat. Extensive cell division was not required for expression of heat tolerance. Membrane fluidity, as determined by the degree of rotational mobility of the fluorescent probe diphenylhexatriene, decreased with increasing growth temperatures, but the relationship did not hold in exponential phase cells grown at 32 degrees C. The cholesterol : phospholipid molar ratio correlated with the fluorescence polarization values, suggesting that the cells are able to adjust membrane fluidity by varying the concentration of cholesterol. The results are compatible with the concept of homeoviscous adaptation: that organisms strive to maintain an optimal level of membrane fluidity and when grown at a different temperature will alter the lipid composition in order to maintain this level. Up until now, cholesterol has not been implicated in this process.

Animals↗
PubMed1981

The role of energy in hyperthermia-induced mammalian cell inactivation: a study of the effects of glucose starvation and an uncoupler of oxidative phosphorylation.

When cultured Chinese hamster cells were exposed to 43 degrees C hyperthermia, effects due to glucose deprivation and to the presence of the uncoupler of oxidative phosphorylation, carbonylcyanide-3-chlorophenylhydrazone, during the 43 degrees C treatment proved to be strongly accelerated compared to the effects at normal temperature (37 degrees C). This strongly indicates that the availability of energy plays an important role in the response of these cells to hyperthermia. One of the reasons cells die after hyperthermia may be a lethal lack of energy. Cells heated before glucose deprivation were able to maintain viability for a longer period during deprivation than cells without the preheat treatment. As the cells might develop thermotolerance after the heat exposure, this suggests that cells in the thermotolerant state use energy in a more economical way.

Animals↗
PubMed1981

Induction of hyperthermia by ultrasound.

Induction of hyperthermia by ultrasound is facilitated by the characteristics of sound absorption in tissue: at frequency of 500 kHz the penetration distance in muscle is about 12.5 cm. Energy deposition patterns can be shaped by focussing or by the use of multiple transducers. An initial clinical study has demonstrated the safety and efficacy of the heating technique. Temperatures of 43-45 degrees for 30-45 min were obtained in surface accessible tumors. 50 per cent of the treated tumors regressed either partially or totally. Normal tissue damage was minimal even in sites that had previously been heavily irradiated. A few patients given relatively small doses of X-irradiation in addition to the hyperthermia responded very well. Based upon these encouraging results, a new ultrasound system designed for heating of deep seated lesions has been built and tested.

Animals↗
PubMed1980

Combined radiation and hyperthermia in superficial human tumors.

Hyperthermia (42--43 C) appears to potentiate the effects of radiation therapy in experimental tumor models. In addition, some studies indicate that tumors may be sensitized to a greater extent than normal tissue. This study was designed to test whether the effectiveness of irradiating human tumors was enchanced significantly by concomitant heating. We also examined skin to see if heating enhanced the response to radiation of normal tissues. Nineteen patients with multiple metastatic superficial tumor masses of various histologies were studied. All were considered incurable and an independent clinical decision had been made to irradiate for palliation. Two or more masses in the same patient were matched for size and location, so that one of the patient's own tumors was a control to monitor the effect of irradiation alone. On each patient the tumors were treated with identical fractions and to the same total dose of radiation. One of the matched nodules was given hyperthermia (43 C) for 15 minutes before and 30 minutes after each radiation fraction. The response of the tumor that received radiation alone was compared with that of the tumor receiving hyperthermia and radiation. In seven of 15 evaluable patients the tumor that received heat in addition to radiation had a greater objective response than the tumor receiving radiation alone (P < .065). Of the remaining eight patients, four had complete tumor regression in both areas without later regrowth, two failed to respond in either area, and two partially responded in both areas. Two patients had increased cutaneous reaction to radiation in the heated area; one of these was a severe desquamative reaction, which conformed to the size and shape of the ultrasound field. These results suggest that hyperthermia improves the objective response to radiation in some human tumors; in two cases it appeared to sensitize skin as well.

Dose-Response Relationship, Radiation↗
PubMed1980

Effects of hyperthermia in a malignant tumor.

The mechanisms of immediate and delayed tumor cell killing by hyperthermia were investigated in EMT-6 neoplasms implanted in BALB/cKa mice. Radiofrequency electromagnetic fields were used to achieve a curative local dose of 44 degrees C for 30 minutes. The tumors were sampled sequentially, during and after heat therapy, and studied by light and elecron microscopy. Assays for cell survival, including cell cultures, were performed at various times after completion of therapy. Focal cytoplasmic swelling, rupture of the plasma membrane and peripheral migration of heterochromatin were observed 5 minutes after initiation of therapy and led to cytoplasmic fragmentation by the end of the treatment period (30 minutes). Necrosis of most cells occurred 2--6 hours after the end of treatment. At 48 hours, there were no recognizable tumor cells. A scar replaced the tumor bed 14 days later. Viable (clonogenic) tumor cells were still 2% of control levels at the end of therapy and then progressively decreased to 0.0003% at 48 hours, confirming the morphologic observations and indicating that factors other than the direct effect of heat on tumor cells contributed to complete tumor eradication. Our findings, coupled with previous studies, suggest that the immediate heat induced necrosis in this tumor occurs through the mechanisms of physical changes in the plasma membrane. The delayed (post-therapy) cell death is likely due to modifications in the environment of the tumor bed.

Animals↗