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J H Jardine

Publications and source records attributed to J H Jardine.

At least 19 recordsLinked to original sources
PubMed1993

Analysis of interleukin-2-activated killer cells of rhesus monkeys: striking resemblance to the human system.

We have found numerous and exquisite homologies between the interleukin-2 (IL-2)-activated killing systems of rhesus monkeys and humans. Lymphocytes with high oncolytic and proliferative activity were generated from peripheral blood, spleen, and bone marrow of monkeys after culture with IL-2. The distribution of lymphocyte subsets in IL-2 cultures closely paralleled that seen in humans, including a decrease in CD4+ and increase in CD8+, CD38+, and CD25+ lymphocytes and an increase in density of CD2 molecules. We also describe three distinct subsets of monkey lymphocytes, CD16+,56-, CD16+,56+"dim", and CD16-,56+"bright", and show that the CD56+"bright" subset is substantially increased (to as high as 79%) after IL-2 activation. Furthermore, as in humans, the cells with oncolytic activity were characterized as CD56+, CD16+/-, and CD8+. This strong homology with humans indicates that the rhesus monkey may be a valuable preclinical model for evaluation of therapeutically relevant biological response modifiers.

Animals↗
PubMed1992

Neutron RBE for primate spinal cord treated with clinical regimens.

The RBEs of high-energy neutrons given in 9 or 12 fractions for cervical spinal cord injury in rhesus monkeys was determined using photons at 2.2 Gy per fraction as the reference radiation. Because the dose-response functions were not parallel, the RBE was not constant but rather increased with dose or, equivalently, with the probability of myelopathy. This required the development of a novel method of determining the RBE versus level of response. The RBE is presented as a function of probability of myelopathy from 0.1 to 99%. At a 50% incidence of myelopathy, the RBE (+/- 1 SE) was 5.22 +/- 0.15. A difference in the histopathology of lesions induced by photon and neutron treatments was observed.

Animals↗
PubMed1990

Modified methodology to improve flow cytometric DNA histograms from paraffin-embedded material.

Flow Cytometric (FCM) DNA content analysis of paraffin-embedded tissues has become a widely accepted procedure in assessing the biologic course in some tumors from archival material. Difficulty in interpreting histograms is frequently due to high levels of debris, and wide coefficients of variation (CV). These may lead to underestimating near-diploid abnormality. Although the clinical significance of low-degree aneuploidy has yet to be established, the procedure reported here improved our endeavor to detect DNA Indices (DI) of at least 1.1%. Experience has shown that careful technique can result in overall improvement of DNA histograms by lowering levels of debris and % CV, dramatically so in some cases. Archival histograms can be generated that rival in quality fresh tissue results. Archival material is currently employed for diagnostic and research purposes.

DNA, Neoplasm↗
PubMed1989

Tumoricidal effect of interleukin-2-activated killer cells in canines.

We investigated the effect of both partially purified (TCGF) and recombinant interleukin-2 (rIL-2) on the tumor-directed cytotoxic activity of canine peripheral blood mononuclear cells (PBMC) using three normal canines. No cytotoxic activity was displayed by unstimulated effector cells at 3 h of incubation; however, the cytotoxic effect was observed in a 16-h assay. PBMC of all canines displayed significant levels of lytic activity after stimulation for 4 to 7 days with both types of IL-2 against a variety of allogeneic and xenogeneic neoplastic cells in 3-h 51Cr release assay. The cytotoxic activity of cultured cells increased proportionally in the 16-h assays. Morphological examination of the May-Grünwald and Giemsa stained cytocentrifuged slides of cultured cells on each day of assay showed an increase in large granular lymphocytes (LGLs) beginning on day 4 and reaching a peak on day 7 of culture.

Animals↗
PubMed1987

Enhanced cardiotoxicity in rabbits treated with verapamil and adriamycin.

Verapamil, a calcium channel blocker, reduces resistance of some tumors to Adriamycin by inhibiting Adriamycin efflux from resistant cells. This study shows that rabbits given 7 mg/kg of Adriamycin and 0.8 mg/kg of verapamil died earlier with functional and morphological cardiac abnormalities than rabbits given Adriamycin alone. Rabbits that were given verapamil and died peracutely had higher concentrations of Adriamycin in the myocardium. The relatively high dose of Adriamycin was expected to produce cardiotoxicity in rabbits within a matter of days. However, peracute death (within hours) in rabbits given the same dose of Adriamycin but with verapamil treatment was unexpected. These results suggest that combining Adriamycin with verapamil increases early cardiac toxicity. Therefore, clinical use of this combination should be approached cautiously until the interactions, including the possibility for enhanced normal tissue damage, are fully understood.

Animals↗
PubMed1987

Epidermal capillariasis in South African clawed frogs (Xenopus laevis).

Significant morbidity and mortality of South African clawed frogs, Xenopus laevis, can be caused by parasitism of the epidermis by a capillarid nematode. These worms produce an erosive dermatitis that is complicated by infection with gram-negative microorganisms. The nematode apparently has a direct life cycle that can be completed within the epidermis of the frog. These characteristics are suggested by the lack of an intermediate host and failure to detect visceral migration. Another unique feature of the parasite was the presence of larvated eggs, in utero. Some have named the parasite Capillaria xenopodis, whereas others called it Pseudocapillaroides xenopi to distinguish it form the typical members of the genus Capillaria.

Animals↗
PubMed1986

Acute and late radiation injury in rhesus monkey parotid glands. Evidence of interphase cell death.

Acute and chronic salivary gland dysfunction are common sequelae of radiotherapy for head and neck cancer; but the associated morphologic changes, especially of the acute damage, have received relatively little study. For investigation of the morphologic characteristics of acute radiation injury to parotid glands, rhesus monkeys were studied 1-72 hours after parotid irradiation with single doses of 2.5-15.0 Gy. The acute damage from all doses was clearly expressed by 24 hours. Histologically, parotid glands irradiated with 2.5 or 5.0 Gy had random degeneration and necrosis of the serous acinar cells. Doses of 7.5-15.0 Gy produced widespread degeneration along with necrosis of whole acini. Serous cell damage was accompanied by neutrophilic inflammation that subsided after 24 hours to become replaced by plasma cell and lymphocytic infiltrates. Parotid glands receiving 7.5-15.0 Gy were atrophic at 16-22 weeks after irradiation and showed no recovery by 40 weeks. Although parotid acinar cells are well-differentiated nondividing cells, these observations show that they express lethal radiation injury in interphase within hours of receiving a radiation dose as low as 2.5 Gy. This is unlike most mammalian cells that express radiation injury during mitosis. Chronic atrophy is a consequence of this direct, irreversible, and early injury, rather than the result of radiation-induced changes in the vasculature.

Acute Disease↗
PubMed1986

Unique radiosensitivity of serous cells in rhesus monkey submandibular glands.

The saliva of patients undergoing radiation therapy for head and neck cancer contains increased acidic mucosubstances associated with a reduced serous component. To assess the morphologic features of the acute radiation damage in serous versus mucous acinar cells, the mixed serous/mucous submandibular glands of 18 rhesus monkeys were studied 1-72 hours after irradiation with single doses of 2.5-15.0 Gy. Selective degeneration and necrosis of serous cells was observed with doses of 2.5-7.5 Gy. Doses of 10.0-15.0 Gy caused widespread destruction of whole serous acini, but only isolated mucous cells were affected. The lesions were clearly expressed by 24 hours. Transient exudation of neutrophils was replaced by plasma cells and lymphocytes. Examination at 16, 22 and at 40 weeks revealed that late atrophy was caused solely by loss of serous acini in glands treated with 7.5 and 10.0 Gy. Although both serous and mucous acini were reduced in glands treated with 12.5 and 15.0 Gy, the atrophy was mainly due to loss of serous acini. The finding that serous cells are more vulnerable to radiation injury than mucous cells provides a morphologic explanation for early and late changes in saliva composition after salivary gland irradiation.

Animals↗
PubMed1985

Natural killer cell-mediated antitumor reactivity of rhesus monkeys.

We have analyzed natural killer (NK) cell-mediated antitumor activity or peripheral blood mononuclear cells of rhesus monkeys. All monkeys displayed significant NK cell cytolytic activity against the human tumor cell lines K-562, Daudi and CEM in a short-term (3 h) 51Cr-release assay. Similar to NK cells described in other species, the cytotoxic cells of monkeys were relatively nonadherent to nylon wool columns, exhibited low density after separation on discontinuous Percoll density gradients, and displayed large granular lymphocyte (LGL) morphology. Analysis of the mechanism of NK cell cytotoxicity of rhesus monkeys demonstrated that on the average, 7.1% (range: 3.1-13.2%) of lymphocytes bound to K-562 tumor, and that approximately 14.8% (range: 7.9-26.3%) of these tumor-binding cells (TBC) were cytolytically active. Examination of TBC on cytocentrifuge slides indicated that the majority of binders displayed LGL morphology. The cytotoxic reaction mediated by monkey NK cells exhibited Michaelis-Menten kinetics pattern; the maximum rate of lysis (Vmax) of K-562 was found to be 1-2 X 10(4) following 3 h of incubation. Using similar culture conditions, the recycling capacity of NK cells of this species was estimated at 2-6 times. Finally, it was observed that the NK cell activity of most monkeys could be potentiated following in vitro exposure to the biological response modifier, interleukin-2.

Animals↗
PubMed1984

Histologic classification as an indication of therapeutic response in malignant lymphoma of dogs.

In retrospective evaluation of treatment of canine malignant lymphoma, 12 of 13 dogs that had received doxorubicin alone or in combination with dacarbazine attained complete remission. Doxorubicin had been given alone, with combination chemotherapy being used only when complete remission could not be achieved and maintained with doxorubicin. The response to single or combined chemotherapy was correlated with histologic cell type of the malignant lymphoma. Histiocytic cell types did not respond to doxorubicin alone, but lymphoblastic types did respond. Combination chemotherapy was effective against histiocytic types. A mixed-cell type, which was initially responsive to doxorubicin alone, but not responsive after relapse, was observed to be histiocytic on rebiopsy.

Animals↗
PubMed1984

Natural killer cell profile of two random-bred strains of athymic rats.

We have demonstrated that Rowett and NIH strains of random-bred athymic and euthymic rats exhibited significant levels of natural killer (NK) cell cytotoxicity against various murine and human tumor cell lines. Rats of both strains displayed high NK cell cytotoxicity in peritoneal exudate, peripheral blood and spleen, and lower activities in lung and liver. No activity was detected in bone marrow. In general, athymic rats manifested higher levels of NK cell cytotoxicity and higher tumor-binding potential than euthymic animals. NK cell cytotoxicity was subject to late maturation and did not decline with age. Cytotoxic cells were not removed by carbonyl iron treatment and resided in both adherent and nonadherent fraction after nylon-wool filtration, with the majority of the cytotoxicity in the latter fraction. Percoll gradient separation studies indicated that, in general, the cytotoxic cells were of large granular lymphocyte morphology and of low density. Evaluation of tumor-binding capacity and cytotoxic profile of large granular lymphocytes has shown that the majority of these cells exhibited cytotoxic potential, but only a minority of them displayed tumor-binding capacity.

Animals↗
PubMed1983

Primary pulmonary fibrosarcoma associated with Spirocerca lupi infection in a dog with hypertrophic pulmonary osteoarthropathy.

A dog with severe subperiosteal cortical thickening in all 4 limbs was found at necropsy to have a small noncircumscribed firm lesion in a lung lobe. Microscopically, the lung lesion was a fibrosarcoma that contained several adult nematodes identified as Spirocerca lupi. Lesions were not found in the esophagus or aorta, which are the typical locations for lesions caused by this parasite. Fibrosarcomas have been associated with S lupi infection in the esophagus. In this case, the nematode localized and reached maturity in an aberrant location and apparently participated in the development of a fibrosarcoma at this site.

Animals↗
PubMed1983

Late effects of 50 MeV d leads to Be neutron and cobalt-60 irradiation of rhesus monkey cervical spinal cord.

The cervical spinal cords of 30 rhesus monkeys were irradiated with 50 MeV d leads to Be neutrons or 60Co gamma rays to evaluate the dose-response relationships for radiation myelopathy. Three groups were treated with 50 MeV d leads to Be neutrons using dosage schedules of 1300 rad n gamma (Group I), 1425 rad n gamma (Group II), or 1550 rad n gamma (Group III) in nine fractions over 29 days. Three groups were irradiated with 60Co gamma rays using dosage schedules of 4620 rad (Group IV), 5390 rad (Group V), or 5940 rad (Group VI) in 22 fractions over 29 days. A significant dose-response relationship was observed for the groups treated with neutrons. Whereas none of the monkeys in Group I showed clinical evidence of neurologic dysfunction, all five animals in Group III became paralyzed. One animal in Group II developed transient neck stiffness and mild unilateral leg paresis. No definitive signs of neurologic injury were seen in any of the animals irradiated with 60Co. The histopathologic changes correlated well with the clinical observations. All of the animals in Group III exhibited moderate to severe malacia and demyelination of the white matter of the cervical spinal cord. The histologic data indicated that the RBE for five times weekly fractionation (approximately 270 rad 60Co fractions) was in the range of 4.2 to 4.6, since the malacia and demyelination in the spinal cords irradiated with 5940 rad of 60Co gamma-rays were greater than that observed in the spinal cords irradiated with 1300 rad n gamma of neutrons but less than the changes in those irradiated with 1425 rad n gamma of neutrons.

Animals↗
PubMed1982

50-MEVd leads to Be neutrons: a comparison of normal tissue tolerance in animals with clinical observations in patients.

The acute and late effects of 50 MeV neutrons were investigated by irradiating a variety of organ systems in large animals using dosage schedules similar to those that have been employed clinically. The RBEs for acute effects in pig skin and rhesus monkey oral mucosa were significantly less than the RBEs for late effects. This observation has also been noticed clinically. The RBEs for late effects in pig skin, rhesus monkey oral mucosa, and rhesus monkey kidney were consistent with values of 3.1 to 3.4 relative to approximately 200 rad 60Co fractions and approximately 2.2 to 2.6 relative to approximately 400 rad 60Co fractions. The RBE for radiation myelitis was significantly greater (4.2 to 4.6 relative to approximately 270 rad 60Co fractions). The tolerance doses for 50 MeVd leads to Be neutrons in large animals were approximately 2200 radn gamma/61/2 weeks for skin contraction, approximately 2100 radn gamma/61/2 weeks for oromucosal necrosis, approximately 1300 radn gamma/41/2 weeks for radiation myelitis, and approximately 960 radn gamma/4 weeks for radiation nephritis. These values correlate well with clinical observations at TAMVEC, since the majority of soft tissue complications in patients occurred following tissue doses in excess of 2100 radn gamma.

Animals↗