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Biomedical subjects

B C Zook

Publications and source records attributed to B C Zook.

At least 19 recordsLinked to original sources
PubMed2001

The effects of 860 MHz radiofrequency radiation on the induction or promotion of brain tumors and other neoplasms in rats.

Sprague-Dawley rats were irradiated with a continuous- wave (CW) or a pulsed-wave (P) radiofrequency (RF) for 6 h/day, 5 days/week from 2 up to 24 months of age. The RFs emanated from dipole antennas (1 W average output) 2.0 +/- 0.5 cm from the tip of each rat's nose. The RFs had an 860 MHz frequency, and the specific absorption rate was 1.0 W/ kg averaged over the brain. Fifteen groups of 60 rats (900 total) were formed from offspring of females injected i.v. with 0 (groups 1, 2, 9, 10, 13), 2.5 (groups 5, 6, 7, 8, 11, 12, 14) or 10 mg/kg (groups 3, 4, 15) ethylnitrosourea (ENU) to induce brain tumors. Groups 1, 3, 5 and 7 received the PRF, and groups 9 and 11 the CWRF; groups 2, 4, 6, 8, 10 and 12 were sham-irradiated, and groups 13-15 were cage controls. All rats but 2, totaling 898, were necropsied, and major tissues were studied histopathologically. There was no statistically significant evidence that the PRF or CWRF induced neoplasia in any tissues. Additionally, there was no significant evidence of promotion of cranial or spinal nerve or spinal cord tumors. The PRF or CWRF had no statistically significant effect on the number, volume, location, multiplicity, histological type, malignancy or fatality of brain tumors. There was a trend for the group that received a high dose of ENU and was exposed to the PRF to develop fatal brain tumors at a higher rate than its sham group; however, the result was not significant using the log-rank test (P = 0.14, 2-tailed). No statistically significant differences were related to the PRF or CWRF compared to controls in the low- or zero-dose groups regarding tumors of any kind.

Animals↗
PubMed2000

Efficacies of BCG and vole bacillus (Mycobacterium microti) vaccines in preventing clinically apparent pulmonary tuberculosis in rabbits: a preliminary report.

Tuberculosis (TB) kills more people in the world today than any other infectious disease, and the number of drug-resistant Mycobacterium tuberculosis isolates is increasing. Vaccines, better than most of the currently available strains of bacille Calmette-Guérin (BCG), are urgently needed to control this disease. TB in rabbits resembles human TB more closely than TB in any other common laboratory animal and a most pertinent method of assessing vaccine efficacy is Lurie's tubercle count method in this species. Vaccinated and control rabbits were infected by aerosol with virulent human-type tubercle bacilli (H37Rv). At necropsy 5 weeks thereafter, the grossly visible primary tubercles in the entire lung were counted. A decrease in the number of such tubercles is a quantitative measure of vaccine efficacy: An effective vaccine prevents microscopic tubercles from growing to grossly visible (clinically apparent) size. The Pasteur substrain of BCG and two substrains of Mycobacterium microti (the vole bacillus) reduced the number of visible primary tubercles an average of 75%, whereas three other substrains of BCG and three other substrains of vole bacilli only reduced the number an average of 40%. These initial studies indicate that Lurie's tubercle-count method in rabbits is a precise way to choose the best available tuberculosis vaccines.

Animals↗
PubMed1999

Virulence of Mycobacterium tuberculosis CDC1551 and H37Rv in rabbits evaluated by Lurie's pulmonary tubercle count method.

The virulence of the CDC1551 strain of Mycobacterium tuberculosis was compared to that of H37Rv in a rabbit inhalation model. While rabbits that inhaled the two strains produced equal numbers of grossly visible primary tubercles, CDC1551 tubercles were smaller and contained fewer bacilli than H37Rv tubercles. These findings suggest that a miniepidemic near the Kentucky-Tennessee border caused by CDC1551 was due not to increased virulence but to increased transmissibility.

Animals↗
PubMed1992

Morphologic effects of fast neutrons or photons on the canine kidney.

Thirty-nine adult male Beagles received either fast neutron or photon irradiation to the right thorax to determine the relative biological effectiveness of fast neutrons on normal pulmonary tissue. The right anterior abdomen, including the cranial half of the right kidney, was included in the field of irradiation. Twenty-four dogs (six/group) received fast neutrons with an average energy of 15 MeV to total doses of 1000, 1500, 2250, or 3375 cGy in four fractions per week for 6 weeks. Fifteen dogs received 3000, 4500, or 6750 cGy of photons (five/group) in an identical fractionation pattern. All 12 neutron irradiated dogs receiving 3375 and 2250 cGy and 1 of 6 receiving 1500 cGy, developed clinical and clinical pathologic signs of hepatic, pancreatic, and gastrointestinal disturbances, but no signs of renal injury were seen. These 13 dogs died or were euthanatized 47-367 days after irradiation. Only 1 of 5 dogs receiving 6750 cGy of photons developed similar signs and died 708 days post-irradiation. The remaining 11 neutron irradiated dogs and 14 photon irradiated dogs eventually died of other causes. All 39 dogs were necropsied and their kidneys were compared to each other and to control dogs. Radiation induced lesions included hemorrhages, necrosis and disappearance of tubular epithelia, glomerulosclerosis, atrophy and fibrosis. These lesions were associated with degenerative and occlusive vascular changes and were much more severe in the neutron irradiated dogs. The relative biologic effectiveness of fast neutrons for canine kidney assessed by gross and microscopic pathology is approximately 4.5 (6750/1500).

Animals↗
PubMed1991

Preclinical and clinical studies on immunogenicity and safety of the HIV-1 p17-based synthetic peptide AIDS vaccine--HGP-30-KLH.

Immunization with a synthetic HIV-1 p17 peptide analog (HGP-30; aa 85-115 of HIV p17), coupled to a carrier protein (KLH, keyhole limpet hemocyanin) given with alum as the adjuvant induces antibodies which cross-react with both HGP-30 and HIV p17 and clones of cytotoxic and helper T-cells which recognize HGP-30 and HIV p17. Proliferation of lymphocytes in response to HGP-30 has been observed in mice, in HIV-infected individuals and in healthy HIV-seronegative volunteers vaccinated with the p17-based synthetic peptide construct. Cytotoxic T-cell responses against EBV transformed, recombinant p17 pulsed targets were observed using antigen-expanded PBLs from HGP-30-KLH immunized individuals. These results are consistent with predictions that the HGP-30 domain of HIV p17 contains both T- and B-cell epitopes that are recognized by animals and humans. In preclinical toxicology studies in animals and in initial clinical trials in humans the synthetic peptide construct (HGP-30-KLH/alum) has been shown to be safe. This paper summarizes the preclinical immunogenicity and safety data for HGP-30-KLH and presents the initial results from the first Phase 1 clinical trial.

AIDS Vaccines↗
PubMed1987

Malignant neoplasms of decidual origin (deciduosarcomas) induced by estrogen-progestin-releasing intravaginal devices in rabbits.

A combination of estrogen and levonorgestrel was continuously delivered to 23 adult rabbits for up to 2 years via a Silastic ring device sutured into the vagina. Twenty-one control rabbits were given similar rings devoid of drugs. A marked decidual reaction of the endometrium occurred in 16 of 23 test rabbits. In 14 test rabbits (61%) malignant tumors developed of decidual type cells not heretofore described. The deciduosarcomas were composed of anaplastic cells that invaded the uterine walls, uterine lymphatics, and in 4 of 13 (31%) rabbits that survived 2 years of treatment, the tumors metastasized to the lungs. Several deciduosarcomas appeared to arise within the spleen or other abdominal organs. Other drug-related lesions included uterine or vaginal polyps, endometrial atrophy, and focal necrosis and mineralization of the uterine wall. Cells from several deciduosarcomas failed to produce tumors in nude mice or to colonize on soft agar. No decidualization or decidual neoplasms were seen in the controls.

Animals↗
PubMed1986

Effects of collagenase and chymopapain on spinal nerves and intervertebral discs of cynomolgus monkeys.

In order to test the safety and efficacy of Nucleolysin, a collagenase for intradiscal chemotherapy, laminectomies were performed on the L2-3 intervertebral discs of four groups of three young adult Cynomolgus monkeys. One primate from each group was injected with half the recommended human dose of Nucleolysin, chymopapain, or the same volume of sterile water. The remaining half of the human dose of each drug or equal volume of sterile water was equally divided and placed upon the right L-3 and L-4 nerve roots at their vertebral foramina. The right L-4 nerve root was first compressed for 10 seconds with an aneurysm clip. These procedures were done to simulate inadvertent contact of enzyme with spinal nerves in patients undergoing chemonucleolysis. After 4 weeks of observation, the 12 primates were humanely killed and examined post mortem. The effects of both enzymes were limited to those tissues with which they came in direct contact. Complete digestion of the nucleus pulposus of all enzyme-injected intervertebral discs was observed. Variable portions of the anulus fibrosus (from 2.3% to 57.4%) were also dissolved. Direct contact of Nucleolysin with lumbar nerve roots caused minor perineural reaction and no more intraneural changes than seen in sterile water controls. Chymopapain induced mild to severe perineural skeletal muscle necrosis and fibrosis with perineural arterial lesions as well as a degenerative neuropathy which was more marked in the traumatized nerve. The results of this study suggest that Nucleolysin and chymopapain are approximately equally effective on intervertebral discs, and that Nucleolysin is less injurious to spinal nerve roots and perineural tissue at the doses used.

Animals↗
PubMed1983

Pathologic findings in rats following inhalation of combustion products of polytetrafluoroethylene (PTFE).

Adult male Fischer 344 rats received single 30-min exposures to the aerosolized products of polytetrafluoroethylene (PTFE) heated to 595 degrees C. The concentrations of thermal degradation products of PTFE were at the LC50 dose of 0.045 mg/l for most rats, but some rats received doses ranging from 0.005 to 5.025 mg/l. Serial measurements of cardiopulmonary function were obtained and will be published subsequently. Necropsies were performed at 0, 2, 12, 24 and 36 h post-exposure, and a few rats were killed between 2 and 17 days. Signs of respiratory impairment were followed by death in some rats. Pathologic findings included focal hemorrhages, edema and fibrin deposition in the lungs. With time focal interstitial thickenings developed due to hypertrophy and hyperplasia of alveolar cells, and macrophages accumulated in alveoli. Thrombosis of pulmonary capillaries was common. Disseminated intravascular coagulation (DIC) occurred in 53% of test rats; its incidence and severity were positively related to the degree of pulmonary damage. Renal infarcts were common due to DIC. No lesions were seen in kidneys or other tissue (except lung and thymus) unless they were affected with DIC. Thymic lymphocytes underwent necrosis in many test and some vehical (warm air) control rats, possibly due to stress. The finding of DIC in PTFE combustion product exposure has not been reported to our knowledge. The toxicity of the thermal degradation products of PTFE requires further study, especially relative to induction of DIC.

Animals↗
PubMed1983

Pathologic effects of fractionated fast neutrons or photons on the pancreas, pylorus and duodenum of dogs.

Thirty-nine adult male Beagles received either fast neutron or photon irradiation to the right thorax to determine the relative biological effectiveness (RBE) of fast neutrons on normal pulmonary tissue. The right anterior abdomen was included in the field of radiation. Twenty-four dogs (six/group) received fast neutrons with an average energy of 15 MeV to total doses of 1000, 1500, 2250 or 3375 rad in four fractions per week for six weeks. Fifteen dogs received 3000, 4500 or 6750 rad of photons (five/group) in an identical fractionation pattern. All neutron irradiated dogs receiving 3375 and 2250 rad and one receiving 1500 rad developed clinical signs of pancreatic, hepatic and gastrointestinal disturbances. The liver enzymes of these dogs became elevated and they died or were euthanatized in extremis 47-367 days after irradiation. Only one 6750 rad photon dog developed similar signs and died 708 days post-irradiation. Five neutron and 10 photon exposed dogs died of other causes. Neutron-induced lesions in the stomach and duodenum included hemorrhages, erosions, ulcerations and fibrosis. Ulcers perforated the GI tract of five dogs. Pancreatic lesions included degranulation and necrosis of acinar cells, fibrosis ans atrophy. Islet cells were not obviously damaged. All lesions were associated with degenerative and occlusive vascular changes. The RBE of fast neutrons, assessed by clinical signs, gross and microscopic pathology, is approximately 3-4.5 for pancreas and about 4.5 for pylorus and duodenum.

Animals↗
PubMed1982

Horizontal nystagmus in methylmercury poisoned squirrel monkeys.

Chronic states of methylmercurialism were induced in squirrel monkey subjects. Principal neurological signs included ataxia, abnormal gait, incoordination and amaurosis. Although slight to moderate vacuolization occurred in supporting cell layers of the cristae and maculae, receptor cell function was essentially normal. Except for a lowered cold threshold, bithermal caloric-induced nystagmus was not significantly different from control values. Pre and postrotatory (Barany chair) tests revealed a reduction only in frequency related variables. The development of spontaneous and positional nystagmus (sometimes with eyes open) coupled with the behavioral signs and the evidence of normal receptor response suggested cerebellar dysfunction. Severe pathologic changes were present in the cerebral cortex, but no lesions were found in the cerebellar cortex. Substantial neuronal degeneration and gliosis, however, were observed in several subcortical nuclei, including cerebellar and vestibular nuclei.

Acoustic Maculae↗
PubMed1981

Neoplasia in fast neutron-irradiated beagles.

One hundred fifty-one beagle dogs were irradiated with either photons or fast neutrons (15 MeV) to one of three dose-limiting normal tissues--spinal cord, lung, or brain. The radiation was given in four fractions per week for 5 weeks (spinal cord), 6 weeks (lung), or 7 weeks (brain) to total doses encompassing those given clinically for cancer management. To date, no nonirradiated dogs or photon-irradiated dogs have developed any neoplasms. Seven dogs receiving fast neutrons have developed 9 neoplasms within the irradiated field. Of the neutron-irradiated dogs at risk, the incidence of neoplasia was 15%. The latent period for radiation-induced cancers has varied from 1 to 4 1/2 years at this time in the study.

Animals↗
PubMed1981

The pathologic effects of fractionated fast neutrons or photons on canine liver.

Thirty-nine adult male purebred beagles received either fast neutron or photon irradiation to the right thorax to determine the effects on pulmonary tissue. The right half of the liver was included in the field of radiation. Twenty-four dogs (six/group) received fast neutrons with a mean energy of 15 MeV to total doses of 1000, 1500, 2250, or 3375 rads in four fractions per week for 6 weeks. Fifteen dogs received 3000, 4500, or 6750 total rads of photons (five dogs/group) in an identical fractionation pattern. All neutron-irradiated dogs receiving 3375 and 2250 rads and one receiving 1500 rads developed clinical signs, hepatic enzyme, and bilirubin elevations, and the dogs died or were euthanized in extremis on postirradiation day 47-291. Signs of liver injury, other than enzyme changes, have not developed to date (1200-1300 days) in the remaining dogs, except in one 6750-rad photon dog that died of hepatic failure on postirradiation day 708. At necropsy, the irradiated right lobes of the liver were atrophic and the nonirradiated left lobes underwent compensatory hypertrophy. Hepatic arterioles and bile ducts were injured in every dog, but no obstructive lesions were observed in hepatic veins. Portal fibroplasia, bile retention, and proliferation of bile ductules was common; the latter two changes also occurred in the nonirradiated lobes. No qualitative differences were observed between hepatic lesions in neutron- versus photon-irradiated dogs. The relative biological effectiveness of fast neutrons for liver damage appears to be no less than 4.5.

Animals↗
PubMed1981

Anatomy of the beagle in cross-section: head and neck.

The transverse anatomy of the head and neck of the Beagle was studied. Cross-sectional preparations were photographed and compared with computerized tomographic scans, freshly prepared dissection specimens, and with skeletal preparations. Anatomic structures were identified by these means with the aid of anatomy texts. A series of labeled photographs were provided as a basis for interpretation of computerized tomography scans.

Animals↗