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Biomedical subjects

D G Baker

Publications and source records attributed to D G Baker.

At least 127 records · Page 7Linked to original sources

The response of previously irradiated skin to combinations of fractionated X radiation, hyperthermia, and cis-diamminedichloroplatinum.

Mouse legs were irradiated with a dose of 30 Gy. After 50 days, when the acute reaction had regressed to a steady state, they were retreated with either 30 Gy of X rays delivered in six fractions over 12 days, six exposures to hyperthermia for 45 min at 42.7 degrees C, six doses of cis-DDP, or a combination of these agents. The maximum skin reactions and the skin reactions integrated over 50 days were determined. The maximum skin response was found when the previously irradiated skin was treated with a combination of X irradiation and hyperthermia. The addition of cis-DDP to this regimen did not result in a further enhancement of the skin reaction. When the second treatment was irradiation alone or cis-DDP alone, the severity of the skin reactions was similar. Injury from the initial radiation dose persisted so that the cytotoxic action of cis-DDP resulted in a level of subacute skin damage that was similar to a second course of X irradiation.

Animals↗

Influence of ultrasound-induced hyperthermia and X-irradiation on the incidence of metastases from a solid tumor.

The KHT sarcoma transplanted into mouse legs was treated by X-irradiation, hyperthermia or a combination of X-irradiation plus hyperthermia. Neither 20 Gy of X-irradiation or hyperthermia for 60 min were effective in controlling the local tumors when used alone. Simultaneous treatments, however, resulted in 22% of the tumors being locally controlled corresponding to a TER of 2.0. Local control was increased when irradiation was given 1 h before or after hyperthermia, TER 2.8 and was maximum, TER 2.9, when the hyperthermia was 0.1 h after irradiation. When the local tumor was controlled by irradiation alone or by irradiation delivered 1 h before or after hyperthermia, all of the metastases that subsequently occurred arose before or during treatment. When tumors were locally controlled by radiation given during or immediately after hyperthermia, metastases developed that must have occurred as a consequence of the treatment. The treatment sequence that resulted in a maximum TER for tumor control did not correlate with the risk of metastatic spread. The timing of the irradiation in relation to hyperthermia may explain some contradictory findings regarding the influence of heat on the incidence of metastases. Hyperthermia did not affect the distribution of anatomic sites involved with metastases or the ratio of lymphatic to hematogenously spread metastases.

Animals↗

Transmission in airway ganglia of ferrets: inhibition by norepinephrine.

We examined the possibility that norepinephrine inhibits transmission in parasympathetic ganglia of the ferret trachea. We impaled ganglion cells on recording microelectrodes and evoked postsynaptic action potentials by stimulating fiber tracts entering the ganglion. When norepinephrine was added to the recording bath, the action potentials were blocked. Phentolamine reversed this block. These results indicate that, by activating alpha-receptors, norepinephrine inhibits transmission in airway ganglia.

Animals↗

Rheumatoid synovial cell morphologic changes induced by a mononuclear cell factor in culture.

Adherent rheumatoid synovial cells in culture produce large amounts of prostaglandin E2 (PGE2) and collagenase. When exposed to a monocyte-derived factor, such cells exhibit marked increases in PGE2 and collagenase production. In addition, cellular morphology becomes more stellate. In the presence of this factor, indomethacin inhibits both PGE2 production and the stellate changes, whereas collagenase production usually continues at a high rate. Addition of PGE2 to cultures reproduces the stellate change as does the cyclic adenosine monophosphate (cAMP) analog 8-bromo-cAMP. Colchicine inhibits morphologic transformation induced by the monocyte-derived factor, whereas cytochalasin B has no effect. It appears that the stellate morphology is dependent upon PGE2-induced cAMP stimulation and is not related to collagenase production per se.

8-Bromo Cyclic Adenosine Monophosphate↗

The response of previously irradiated skin to combinations of X radiation and ultrasound-induced hyperthermia.

Areas of skin approximately 1.5 cm in diameter on the legs of mice were made hyperthermic (30 min at 42.7 degrees C) by exposure to an ultrasound beam (780 kHz), a single dose of X irradiation (2000 rad), or a combination of these treatments. After 35 days, when the acute reaction had reached a steady state, the same tissue was given a second treatment by either hyperthermia, irradiation, or a combination of hyperthermia and irradiation. When the first treatment was irradiation and the second treatment was either irradiation or a combination of hyperthermia and irradiation, the acute skin reactions were similar to those of skin not previously irradiated, indicating a large proportion of recovery from the first irradiation. When irradiation was the first treatment, a comparison of second treatments by hyperthermia plus irradiation with irradiation alone showed a thermal enhancement of 1.45. When the first treatment was hyperthermia plus irradiation, a comparison of second treatments by hyperthermia plus irradiation with irradiation also showed an enhancement factor of 1.45 for the combined treatment.

Animals↗

The role of polyamine biosynthesis in hematopoietic precursor cell proliferation in mice.

Under the influence of a selective irreversible inhibitor of ornithine decarboxylase (ODC), DL-alpha-difluoromethylornithine (DFMO), early hematopoiesis was enhanced. In the bone marrow, the absolute number of cells that give rise to spleen colonies in lethally irradiated mice (CFU-S), granulocytic colonies in diffusion chambers in mice (CFU-DG), and granulocyte-monocyte colonies in agar in vitro (CFU-C) was increased 2-4 fold. This could be abrogated by administration of putrescine, confirming the association of the stimulatory effect with polyamine biosynthesis most likely via depression of ornithine decarboxylase activity and subsequent synthesis of putrescine. Analysis of cell cycle characteristics by 3H-TdR suicide technique demonstrated that the proportion of CFU-S, CFU-DG, and CFU-C in S-phase was significantly increased. Additionally, the stimulatory effect was reflected by enhanced colony formation in diffusion chambers implanted intraperitoneally in mice receiving DFMO. This could also be eliminated by treatment of the host animal with putrescine, again suggesting that polyamine biosynthesis plays an important role at the early stages of hematopoiesis in vivo. Effect of DFMO on colony formation in vitro (CFU-C) was inhibitory and not reversible with putrescine. It could be partially eliminated by aminoguanidine, which neutralizes diamine oxidase present in fetal calf serum used in the CFU-C assay. These data suggest that the effect of DFMO in vitro was nonspecific.

Animals↗

Effect of ultrasound-induced hyperthermia and cis-diamminedichloride platinum II on murine renal function.

Murine renal function was evaluated after ultrasound-induced kidney hyperthermia (42.5 degrees C and 46.5 degrees C for 35 minutes) and the administration of cis-diamminedichloride platinum II (8 mg/kg). A quantitative immunonephelometric technique was employed to determine urinary total protein (TP) and albumin (Alb) 1-180 days post-treatment. Hyperthermia of 46.5 degrees C elevated urinary TP excretion significantly more than that of 42.5 degrees C cis-diamminedichloride platinum (Cis DDP) administration greatly increase urine TP with a peak mean TP concentration of 488 microgram/ml, four days after Cis DDP (normal range was 26-48 microgram/ml). This returned to normal by day 14. The TP excretion after 42.5 degrees C hyperthermia with concurrent Cis DDP was similar to Cis DDP alone, implying there was no potentiation of early or late Cis-DDP-induced renal damage by hyperthermia. Late mouse mortality was greater (P = 0.08) after Cis DDP alone, than Cis DDP with 42.5 degrees C hyperthermia. There was a statistically significant increase (P less than 0.05) in the Alb/TP excretion ratio after the addition of 42.5 degrees C hyperthermia to Cis DDP, implying an alteration in the site or nature of the Cis DDP renal lesion by hyperthermia.

Albuminuria↗

The radiobiological basis for tissue reactions in the oral cavity following therapeutic x-irradiation. A review.

The radiobiological basis for the response of tissues in the oral cavity following therapeutic doses of ionizing radiation has been reviewed. Clinical manifestations of radiation response occur when the functional compartment of the tissue, the parenchymal cells, is depleted to some minimal value. The time course and severity of the response depend on the sensitivity of cellular compartments, the vegetative intermitotic compartment being the most sensitive and the fixed postmitotic cells being the least sensitive. Early responses are therefore seen in rapid cell renewal systems while the chronic effects are closely correlated with damage to the terminal vascular bed, a multipotential connective tissue compartment. Osteonecrosis of bone following irradiation involves a series of events, including a decreased salivary gland function, devitalization of bone, and infection. Carcinogenesis in oral cavity tissues is a very rare late sequela of therapeutic radiation.

Dental Caries↗

Local thermodilution: a reliable technique for estimating renal blood flow in the rabbit.

1. A thermistor probe designed for determination of renal blood flow in rabbits, consisted of a fast-responding bead thermistor and an injection port which was also used to measure renal venous pressure between injections. 2. By an in vitro calibration system, actual measured flow (Qa) correlates well with the thermodilution calculated flow (Qc), where Qc = 0.99 Qa + 4.9 (r = 0.97, n = 42). 3. The renal blood flow (RBF) as determined by the thermodilution technique in 3 control groups was 53 +/- 3 (8), 60 +/- 6 (8), and 62 +/- 3 (3) ml/min/kidney or about 9% of the cardiac output. 4. Hypovolemia (-10%) reduced RBF by 19% from the control value, whereas, hypervolemia (+10%) did not alter RBF. 5. Smoke-induced apnea resulted in hypertension (+30%) and bradycardia (-39%), and was associated with changes in RBF (-55%) and renal vascular resistance (+183%). 6. We conclude that the local thermodilution technique is a relatively easy and reliable method for estimating RBF in rabbits.

Animals↗

The response of kidney to ionizing radiation combined with hyperthermia induced by ultrasound.

Mouse kidneys were made hyperthermic (42.5 degrees C for 30 min) one hour before, during, or one hour after local irradiation to determine the effect of hyperthermia on radiation damage. An ultrasound beam was used to induce hyperthermia. The urinary concentrations of total protein and albumin were used as criteria of kidney injury. Hyperthermia alone did not induce proteinuria. Radiation alone produced proteinuria that was not correlated with dose. Hyperthermia induced during or after irradiation resulted in a thermal enhancement factor of 1.29 +/- .33. Hyperthermia induced one hour before irradiation resulted in a thermal enhancement factor of 0.88 +/- .05, indicating a radioprotective effect. To the authors' knowledge, this is the first time such an effect has been shown.

Albuminuria↗

Tracheal contraction and relaxation initiated by lung and somatic afferents in dogs.

Capsaicin injected into the right heart of dogs causes reflex bronchoconstriction by stimulating pulmonary C-fibers, but injected into the left heart it is said to have little effect even though it stimulates bronchial C-fibers, which are known to cause contraction of airway smooth muscle. Attempting to resolve this apparent contradiction, we recorded smooth muscle tension in an innervated tracheal segment in anesthetized dogs and examined the reflex effects of injecting capsaicin intravascularly at different sites. Right atrial injection of capsaicin (10 micrograms/kg) caused tracheal contraction, as did bronchial arterial injection (0.15-5.0 micrograms); left atrial injection (10 micrograms/kg), however, caused relaxation or slight contraction, or a combination of the two. Contraction but not relaxation was abolished by cutting or cooling (0 degree C) the cervical vagus nerves. Femoral arterial injection (10-100 micrograms) caused tracheal relaxation, which was abolished by cutting hindlimb nerves. We conclude that both pulmonary and bronchial C-fibers evoke tracheal contraction, but when capsaicin is injected into the left atrium any effects of stimulating bronchial C-fibers are masked by the reflex action of somatic afferents, which cause tracheal relaxation.

Animals↗

Reflex tracheal contraction induced by stimulation of bronchial C-fibers in dogs.

Bradykinin stimulates the afferent vagal endings of bronchial C-fibers but has little effect on other pulmonary vagal afferents. In anesthetized dogs with open chest, we recorded transverse tension in the posterior wall (trachealis muscle) of an upper cervical tracheal segment and stimulated bronchial C-fibers selectively by injecting bradykinin (19 ng-3 microgram) into a bronchial artery. The recurrent and pararecurrent laryngeal nerves were cut so that the superior laryngeal nerves provided the motor supply to the segment. Bradykinin caused a dose-dependent increase in tracheal muscle tension and often a conspicuous decrease in heart rate, which were abolished by vagotomy or administration of atropine. Injection of bradykinin still evoked tracheal contraction when myelinated lung afferents were blocked by cooling the midcervical vagi to 7 degrees C, but contraction was abolished when unmyelinated lung afferents were blocked by cooling to 0-1 degrees C, the effects of cooling being reversible. Our results indicate that stimulation of bronchial C-fibers, like that of pulmonary C-fibers, evokes reflux contraction of airway smooth muscle and reflex cardiac slowing.

Animals↗

Temperature-dependent inhibition of murine granulocyte-monocyte precursors.

The response of nucleated bone marrow cells from C3H mice to hyperthermic temperatures of 41.5 to 49.5 degrees for a fixed heating period of 30 min has been determined. The threshold temperatures for cell lysis, loss of trypan blue exclusion, and histological evidence of cell injury were greater than 49.5 degrees, 45.5 degrees and 43.5 degrees, respectively. Growth of mature granulocyte-monocytes from precursors was evaluated in Millipore diffusion chamber culture. There was a biphasic decrease in granulocyte-monocyte growth after exposure to temperatures of 41.5 to 45.5 degrees. The ratio of granulocytes to monocytes in proliferated cultures was not altered after hyperthermia. Pluripotent and committed granuloid stem cells were assayed by the spleen colony and plasma clot diffusion chamber techniques. These also showed a biphasic decrease with increase in temperature, with committed stem cells having a greater thermal sensitivity at lower temperatures.

Animals↗

Medical radiation exposure and genetic risks.

Everyone is exposed to background radiation throughout life (100 mrem/year to the gonads or 4 to 5 rem during the reproductive years). A lumbosacral series might deliver 2,500 mrem to the male or 400 mrem to the female gonads. A radiologic procedure is a cost/benefit decision, and genetic risk is a part of the cost. Although cost is usually very low compared to benefit, if the procedure is unnecessary then the cost may be unacceptable. On the basis of current estimates, the doubling dose is assumed to be 40 rem (range 20 to 200) for an acute dose, and 100 rem for protracted exposure. Although there is no satisfactory way to predict the size of the risk for an individual exposed, any risk should be incentive to avoid unnecessary radiation to the gonads. Conception should be delayed for at least ten months for women and three or four months for men after irradiation of the gonads. The current incidence of genetically related diseases in the United States population is 60,000 per million live births. Based on the most conservative set of assumptions, an average gonadal dose of 1,000 mrem to the whole population would increase the incidence of genetically related diseases by 0.2%.

Abnormalities, Radiation-Induced↗