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Biomedical subjects

K N Gray

Publications and source records attributed to K N Gray.

At least 19 recordsLinked to original sources

Correlation of kidney weight and volume and selected skeletal parameters to sex in the adult rhesus monkey (Macaca mulatta).

This report outlines a comparison of renal weight and volume and selected skeletal parameters to sex in 22 adult male and 156 adult female rhesus macaques. Means and standard deviations for kidney weight and volume, body weight, and radiographic measurements for both males and females are reported. Ninety-five percent confidence intervals and P-values for the mean differences between the sexes for these parameters were also compiled. Male monkeys were larger, but had kidneys of similar size to those of the females. Joint distributions of the radiographic measurements of the first lumbar vertebra and the skull showed that males were larger in both measurements. The distributions of these parameters were clearly separate in males and females, while joint distributions of kidney weight and volume for males and females overlapped almost completely. We found that, regardless of age, sex, weight, or skeletal size, all normal adult rhesus monkeys generally have similar-sized kidneys.

Animals↗

Postirradiation sarcomas in Sprague-Dawley rats.

A series of radiation-induced neoplasms occurred in Sprague-Dawley rats 4-8 months after irradiation of a single hind leg with 60Co gamma rays. The rats were exposed to fractionated cumulative doses that ranged from 0 to 106 Gy. Osteosarcomas, malignant fibrous histiocytomas and fibrosarcomas developed in the radiation fields of a number of the rats in the higher-dose groups. Tumors did not develop throughout an 8-month observation period in rats that received doses of only 0 or 46 Gy. The most common postirradiation sarcomas in humans are osteosarcoma, malignant fibrous histiocytoma and fibrosarcoma. The Sprague-Dawley rat may serve as a good animal model in studying the development of sarcoma in humans after regional radiotherapy.

Animals↗

Stenosing colonic adenocarcinoma in a female rhesus monkey.

Laparoscopic surgery was performed on a 16 year-old female rhesus monkey presenting with chronic lethargy and inappetence. The procedure revealed a "napkin-ring" stricture located in the ascending large colon. Histologic evaluation of the colonic lesion exhibited large numbers of irregular acini lined by a single layer of well-differentiated neoplastic epithelial cells. Based on the gross and histopathologic findings a diagnosis of adenocarcinoma of the proximal colon was made.

Adenocarcinoma↗

Visual laser ablation of the canine prostate with a diffusing fiber and an 805-nanometer diode laser.

BACKGROUND AND OBJECTIVE: Although the popularity of visual laser ablation of the prostate (VLAP) as a treatment for symptomatic, benign prostatic hyperplasia (BPH) is increasing, the perceived advantages of VLAP over conventional transurethral electroresection of the prostate (TURP) is being debated because optimal technique and dosimetry for surgical lasers are still being refined. At this time, the 1.06 neodymium:yttrium-aluminum-garnet (Nd:YAG) laser and a laterally deflecting delivery system is the hardware combination most widely used for VLAP. STUDY DESIGN/MATERIALS AND METHODS: Reported here is a study of an alternate system, a 805-nm diode laser (Diomed 25 Diomedics, The Woodlands, TX) with a cylindrically diffusing fiber (Surgimedics Inc., The Woodlands, TX). Eight mongrel dogs were prostatectomized by transurethral irradiation of the prostate with 15,000 J of diode laser energy delivered via a fiber that diffuses the energy in a 1.5-cm-long cylindrical pattern. The dogs were sacrificed and prostates harvested at 3 hours and 1,4,7,14,21,35, and 49 days after the procedure, fixed with 10% buffered formalin, and examined histologically. RESULTS/CONCLUSIONS: It was found that this laser/fiber combination created volumes of tissue coagulation similar to those encountered in our previous work with the Nd:YAG laser in combination with both laterally deflecting and diffuser fibers, while offering the distinct advantages of simplified technique, lower cost hardware, and fewer postoperative complications in the dog model.

Animals↗

Radiation response of the monkey kidney following contralateral nephrectomy.

PURPOSE: The long-term functional and morphologic responses of the hypertrophied monkey kidney after unilateral nephrectomy to fractionated irradiation were assessed. METHODS AND MATERIALS: The right kidney of 13 adult female rhesus monkeys was removed. Twelve weeks after unilateral nephrectomy (UN) the remaining kidney received fractionated doses of gamma-rays ranging from 35.2 Gy/16 fractions (F) up to 44 Gy/20 F. Glomerular filtration rate, effective renal plasma flow, blood urea nitrogen, serum creatinine, and hematocrit values were measured up to 107 weeks postirradiation (PI). The monkeys were killed and the remaining kidneys were removed 107 weeks PI or earlier when end-stage renal failure was exhibited. Glomeruli were scored for the presence/absence of several pathologic features including increased intercapillary eosinophilic material (ICE), ectatic capillaries, and thrombi. The relative proportion of renal cortex occupied by glomeruli, interstitium, normal tubules or abnormal tubules was determined using a Chalkley point grid. These quantal dose response data were analyzed using a logistic regression model. RESULTS: Irradiation of the remaining kidney in UN monkeys resulted in a dose-dependent reduction in renal function and anemia. Glomerular dysfunction preceded tubular dysfunction. Animals receiving 44 Gy all manifested progressive clinical renal failure. Conversely, those receiving < or = 39.6 Gy showed stable, albeit impaired, renal function for the duration of the observation period of 107 weeks. Morphologically, the incidence of ICE, ectatic glomerular capillaries, thrombi, and periglomerular fibrosis was significantly dose-related (p < 0.005). A significant (p < 0.001) dose-related increase in the relative proportion of renal cortex occupied by abnormal tubules was indicative of tubular injury. A highly significant (p < 0.001) dose-dependent increase in the proportion of abnormal to normal tubules was also seen. CONCLUSION: The pathogenesis of radiation nephropathy is difficult to fully understand because of the complex and dynamic interactions among all components of the nephron that make discrimination between primary radiation effects and secondary pathophysiological consequences very difficult. Notwithstanding, the current experiment shows that the functional and morphological expressions of radiation injury in the kidney are dose dependent. Renal failure occurs when both the glomeruli and tubules are dysfunctional. In monkeys following UN, a total dose of 44 Gy to the remaining kidney damages all components of the nephron and causes renal failure in less than 45 weeks. With lower doses, changes to the glomeruli predominate and the animals survive. Kidney doses of up to 39.6 Gy/18 fractions of 2.2 Gy are compatible with survival for at least 2 years in primates.

Animals↗

Glands of the eyelids of rhesus monkeys (Macaca mulatta).

The various glands of rhesus monkey eyelids and human eyelids are similar. Numerous modified sebaceous glands are located along the tarsus. These conform with the meibomian glands, while typical sebaceous glands associated with the hair follicles of the lashes are consistent with the glands of Zeis. Lobules of accessory lacrimal tissue, corresponding to the glands of Krause and Wolfring, are located in the conjunctiva of the fornix and along the orbital border of the tarsal plate. Goblet cells are plentiful in the mucosa of the palpebral and bulbar conjunctiva, and along the lid margin are the sweat glands of Moll.

Animals↗

Acute radiation injury of ocular adnexa.

Eyelids and lacrimal glands of monkeys examined histologically 24 and 48 hours after receiving 2.5 to 20.0 Gy (250 to 2000 rad) of cobalt 60 radiation contained acute inflammation. Cells of meibomian glands, other sebaceous glands, sweat glands, and goblet cells displayed no significant alterations. Acinar cells of major and accessory lacrimal glands and, to a lesser degree, lacrimal duct epithelium showed degeneration and necrosis that were increased in extent in proportion to the radiation dose. Reduced numbers of serous acini and decreased size of remaining acini indicate that atrophy of lacrimal glands can be recognized within two days after irradiation. The morphologic diagnosis for irradiated lacrimal glands was acute, necrotizing dacryoadenitis.

Acute Disease↗

Anatomy of the major lacrimal gland of rhesus monkeys (Macaca mulatta).

The major lacrimal gland of rhesus monkeys is impalpable within the fatty connective tissue of the upper lateral quadrant of the orbit. Acini of the lacrimal glands are composed of both sparsely and heavily granulated cells that histochemically resemble serous acinar cells of the submandibular salivary gland. The cytoplasmic granules are strongly periodic acid-Schiff (PAS)-positive, and some are also stained by alcian blue for acidic mucosubstances. The lacrimal gland has a simple duct system of intralobular ducts and interlobular excretory ducts. Lymphocytes and plasma cells are common in the periductal stroma. Major lacrimal glands of rhesus monkeys are suitable for comparative and correlative studies of lacrimal and salivary diseases and radiation responses.

Animals↗

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↗

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↗

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↗

Mobilization of canine hemopoietic stem cells by pyran copolymer (NSC 46015).

Pyran copolymer (NSC 46015), a divinyl ether maleic anhydride of broad spectrum molecular weight, was infused into six normal mongrel dogs. The effect on canine blood and bone marrow colony forming units in culture (CFU-C) was followed over an 11-day period. Significant elevation of circulating CFU-c was noted 2 days after pyran infusion; normalization occurred by day 7 postinfusion. Bone marrow CFU-C were decreased 2 days and 5 days after pyran administration. A further increase in circulating CFU-C was noted when pyran was administered twice, 5 days apart. The mobilizing effect of pyran copolymer appears promising enough to warrant further exploration of blood as a source of hemopoietic stem cells for transplantation purposes.

Animals↗

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↗

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↗