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Biomedical subjects

E J Dick

Publications and source records attributed to E J Dick.

At least 19 recordsLinked to original sources

Endometriosis involving the ileocaecal junction with regional lymph node involvement in the baboon--striking pathological finding identical between the human and the baboon: a case report.

The baboon is an established model for endometriosis research. This report describes the occurrence of spontaneous endometriosis involving the ileocaecal junction and associated regional lymph nodes in the baboon. All endometriotic foci lacked the nuclear atypia, abnormal mitotic activity and altered nuclear-to-cytoplasmic ratio typical of malignancy. These findings are identical to reports in the human in which ileocaecal and colonic endometriosis is associated with endometriosis in pericolonic and mesenteric lymph nodes. The similarity between baboon and human colonic endometriosis in both location and pathology is striking and lends further evidence supporting the validity of the baboon as a model for human endometriosis.

Animals↗

Abdominal pregnancy in a baboon: a first case report.

The abdominal pregnancy is a rare, but life threatening complication of ectopic embryo implantation. Only three cases of abdominal pregnancy have been previously described in primates: in a squirrel monkey, owl monkey and in a rhesus macaque. A 14-year-old wild-caught olive baboon (Papio cynocephalus anubis) was diagnosed at the ultrasound examination with advanced gestational age extrauterine pregnancy. At the initial laparotomy and necropsy the diagnosis of abdominal pregnancy was made on Studdiford's criteria. This case indicates the possibility of developing a model for further study of different types of ectopic pregnancy and indicates a cesarean section as a risk factor for abdominal pregnancy.

Animals↗

The use of a hemoglobin-based oxygen-carrying solution (HBOC-201) for extracorporeal membrane oxygenation in a porcine model with acute respiratory distress syndrome.

OBJECTIVE: To evaluate whether hemoglobin-based oxygen-carrying solution (HBOC)-201 (Biopure) is an effective alternative to donor blood for extracorporeal membrane oxygenation support in a porcine model of acute respiratory distress syndrome (ARDS). DESIGN: Randomized animal clinical trial. SETTING: Animal surgical research laboratory. SUBJECTS: Immature Yorkshire swine were assigned to one of three groups: 1, noninjured animals, donor porcine blood primed circuit; 2, ARDS-injured, HBOC-201 primed circuit; or 3, ARDS-injured, donor blood primed. INTERVENTIONS: ARDS injury was induced in groups 2 and 3 with oleic acid infusion before bypass. All animals were placed on full venoarterial extracorporeal membrane oxygenation support for 8 hrs. MEASUREMENTS AND MAIN RESULTS: Physiologic variables and laboratory samples were measured at baseline and hourly for 8 hrs. Data analysis consisted of repeated-measures analysis of variance with post hoc analysis. We found that 100% of animals survived on extracorporeal membrane oxygenation for the duration of the study period. HBOC-supported animals had comparable oxygen delivery to both donor blood groups. Mean pulmonary artery pressure, heart rate, and lactate concentrations were higher in the injury groups. Blood pressure was mildly increased in HBOC animals (p <.05 vs. control animals). Methemoglobin concentrations in the HBOC group were elevated and increased over time on extracorporeal membrane oxygenation (p <.001). CONCLUSIONS: HBOC-201 appears to be an effective alternative circuit-priming agent for use during extracorporeal membrane oxygenation. HBOC offers the advantages of rapid availability and diminished donor blood cell exposure. The efficacy of HBOC in longer duration bypass, and its associated methemoglobinemia, need to be further investigated.

Analysis of Variance↗

Record review of baboons with histologically confirmed endometriosis in a large established colony.

Spontaneous endometriosis was diagnosed in 43 baboons over a 14-year period. Thirty-seven have died; five remain alive; one was sold and lost to follow-up. The average age at diagnosis was 17.2 years; 29 (67%) were between 12 and 21 years of age. Fifteen (35%) were diagnosed by biopsy and received surgical excision of the endometriotic tissue; four of these were identified during caesarian section, confirming one prior report of endometriosis in pregnant animals. Twenty-eight (65%) were diagnosed at or shortly preceding necropsy. When diagnosed by a palpable abdominal mass, there was a significantly greater likelihood the animal died or was killed as a result of complications of endometriosis. When diagnosis was at necropsy, there was a significantly greater likelihood that the animal died from causes unrelated to endometriosis. Early identification with surgical removal appears to provide a benefit for both survival and delivering offspring after diagnosis. In twenty-one baboons (49%), endometriosis affected multiple sites within the peritoneal cavity. In the remaining baboons, lesions were more localized. Ovarian involvement was seen in sixteen (37%) of these baboons. This paper is the first to describe significant ovarian involvement in baboons, previously considered a limitation of the usefulness of this species as an animal model. We also describe the first reported endometriosis seeding of an abdominal surgery scar in a baboon. Many of these baboons were middle aged, had few or no offspring, or had evidence of a long duration of uninterrupted menstrual cycles, consistent with risk factors for women. Endometriosis was an incidental finding in 17 (40%) of these baboons, consistent with previous reports of minimal endometriosis as a common asymptomatic finding in baboons and in women. Overall, endometriosis in baboons presents a spontaneously occurring animal model that shares important features with the disease in women and the rhesus macaque.

Age of Onset↗

Lack of effect of 94 GHz radio frequency radiation exposure in an animal model of skin carcinogenesis.

Although there is no evidence that electromagnetic energy in the radio frequency radiation (RFR) band is mutagenic, there have been suggestions that RFR energy might serve as either a promoter or co-promoter in some animal models of carcinogenesis. Recent developments in electromagnetic technology have resulted in the manufacture of RFR sources capable of generating frequencies in the millimeter wavelength (MMW) range (30-300 GHz). Because absorption of MMW energy occurs in the skin, it is to be expected that long-term detrimental health effects, if any, would most likely be manifest in the skin. In this study we investigated whether a single (1.0 W/cm(2) for 10 s) or repeated (2 exposures/week for 12 weeks, 333 mW/cm(2) for 10 s) exposure to 94 GHz RFR serves as a promoter or co-promoter in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced SENCAR mouse model of skin carcinogenesis. Neither paradigm of MMW exposure significantly affected papilloma development, as evidenced by a lack of effect on tumor incidence and multiplicity. There was also no evidence that MMW exposure served as a co-promoter in DMBA-induced animals repeatedly treated with 12-O-tetradecanoylphorbol 13-acetate. Therefore, we conclude that exposure to 94 GHz RFR under these conditions does not promote or co-promote papilloma development in this animal model of skin carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

Acute ocular effects of mustard gas: ultrastructural pathology and immunohistopathology of exposed rabbit cornea.

Whole-body exposure to sulfur mustard (HD) produces cutaneous, respiratory and ocular impairment. Of these, ocular damage causes the most immediate incapacitation. Heretofore, characterization of HD ocular toxicity has been largely limited to gross and histological observations. In the present study we explore histological, ultrastructural and immunopathological acute effects of HD ocular exposure and establish correlations with HD toxicity data already documented for dermal exposure. Anesthetized rabbits were exposed to 0.4 microl of liquid HD placed directly on the cornea. Animals were euthanized at 6, 9 and 24 h post-exposure and the eyes were enucleated and processed for histopathology, ultrastructural and immunoperoxidase study. At 6 and 9 h, the most prominent histological feature was nuclear pyknosis, necrosis and loss of polarity of corneal epithelial basal cells to the exclusion of other epithelial cells. At 24 h, all corneal epithelial cells presented degenerative changes, with the epithelium eventually detaching from the underlying basement membrane at the level of the lamina lucida. Microblisters, a characteristic HD-induced skin pathology of the basement membrane zone of animals, were absent in this corneal study. Edema, degenerating fibroblasts and inflammatory cellular infiltrates were persistent stromal responses. Immunopathological effects included changes in antigenicity of bullous pemphigoid protein, laminin, desmosonal protein, Ki67 and p53. These morphological and immunopathological effects of corneal exposure to HD appear to be largely consistent with that previously reported for dermal exposures, perhaps providing shared anatomical considerations for the development of specific HD prophylaxis and therapy.

Administration, Cutaneous↗

Microvascular effects of oral interleukin-6 on ischemia/reperfusion in the murine small intestine.

Oral administration of interleukin-6 (IL-6) has been shown to reduce hemorrhage-induced bacterial translocation from the gut in mice and rats. To examine the intestinal microvasculature, mice were given the electron-dense tracer horseradish peroxidase (HRP) after hemorrhage and IL-6 or vehicle administration. In normal mice and in those hemorrhaged and given IL-6, the electron-dense marker, administered intravenously, could be found in intestinal capillaries and between mucosal epithelial cells, suggesting that the microvasculature was patent. In mice given saline after shock, however, no marker was present in the gut, suggesting that the intestinal microvasculature was unable to deliver the marker to the epithelia. When mice were given HRP intralumenally (il) the tracer was able to penetrate between intestinal epithelial cells only in mice given vehicle after hemorrhage. This finding suggests that hemorrhaged mice were susceptible to sepsis and endotoxic shock from the leaky gut. In normal and IL-6-treated mice, the tracer was unable to pass from the lumen between mucosal epithelial cells, because the presence of an intact zonula occludens prevented passage. Functional studies supported the electron microscopy findings. Bacteria were cultured from the livers of mice fed vehicle after hemorrhage, but not from those fed IL-6. These data support the conclusions that parts of the intestinal microvasculature remain diminished after hemorrhage and resuscitation and that oral IL-6 restores this circulation.

Administration, Oral↗

Histopathologic changes in the brain, heart, and skeletal muscle of rhesus macaques, ten days after exposure to soman (an organophosphorus nerve agent).

BACKGROUND AND PURPOSE: Soman, an organophosphorus, anticholinergic, chemical warfare nerve agent, is studied at few research facilities, and there have been few pathologic studies of soman-exposed primates. We describe the brain, heart, and skeletal muscle lesions, review lesions described in literature, and discuss possible pharmacologic mechanisms for soman-induced neuron necrosis. METHODS: In this retrospective, histopathologic study, records were obtained for 36 rhesus macaques (Macaca mulatta) that were euthanized 10 days after soman exposure, from a larger group of 103 monkeys that were exposed to soman and used for pharmacologic and lethality studies. RESULTS: Brain lesions were seen in 9 of 15 animals that convulsed and in only 1 of 21 that did not convulse. The brain lesions in our primates were limited to the hippocampus, amygdala, and thalamus (of one animal), and consisted of neuron necrosis and dropout, spongiosis, gliosis, astrocytosis, and vascularization. Heart lesions consisted of myocardial degeneration and necrosis. Three animals had brain and heart lesions, 7 had brain lesions only, and 3 had heart lesions only. Skeletal muscle lesions, although minimal to mild, were in most of the animals, whether they had convulsed, but most had muscular tremors. These lesions were in the biceps brachii (11 of 22 monkeys), anterior tibialis (8/22), biceps femoris (7/22), flexor carpi radialis (5/22), gastrocnemius (3/22), and diaphragm (1/22). The limited literature on soman lesions in primate brain and heart, and the limited information on skeletal muscle lesions, is reviewed. CONCLUSIONS: Brain lesions were not as wide-spread as reported in other studies of primates and rodents, and were significantly associated with convulsions. Unlike other studies using rodents, we observed poor correlation between heart and brain lesions; thus, a single hypothesis to explain the pathogenesis for the brain and heart lesions may be difficult to establish.

Animals↗

Differentially increased IL-6 mRNA expression in liver and spleen following injection of liposome-encapsulated haemoglobin.

Injection of the red cell substitute liposome-encapsulated haemoglobin (LEH) induces increased serum interleukin (IL)-6 in the absence of other inflammatory cytokines. In vitro studies found that IL-6 mRNA was increased in Mphi and endothelial cell lines by co-culture with LEH. In the present study, cytokine mRNA expression in extracts of livers, spleens, lungs and kidneys after LEH injection was determined by semi-quantitative RT-PCR. The distribution of cells expressing IL-6 mRNA in livers and spleens was visualized by in situ hydridization; extracts of kidney and lung did not show increased IL-6 mRNA and were not studied further. IL-6 mRNA accumulation in livers and spleens was increased at 4 h following LEH injection and had declined by 24 h. In the liver, cells expressing IL-6 mRNA were located in endothelia of hepatic and portal veins, and hepatic sinuses, Kupffer cells and epithelial cells of bile ducts. Endothelium of hepatic arteries did not express IL-6 mRNA. Lymphocytes, haematopoietic cells and macrophages expressed IL-6 mRNA in spleens. The data suggest that cells of the reticuloendothelial system (RES) might be a significant source of increased plasma IL-6 in vivo after LEH administration.

Animals↗

Acute and long-term response of the meniscus to partial meniscectomy using the holmium: YAG laser.

The purpose of this study was to evaluate the histological effects of holmium:YAG laser partial meniscectomy in an in vivo rabbit model and compare it with scalpel partial meniscectomy at selected time intervals. Twenty-four adult male New Zealand rabbits underwent bilateral partial medial meniscectomies through the avascular zone. In the right knee, partial medial meniscectomy was performed using a standard surgical blade; in the left knee, an anatomically similar partial medial meniscectomy was performed using a Ho:YAG laser (Coherent, Santa Clara, CA). All animals were randomized and three animals were killed at postoperative days I and 3, and postoperative weeks 1, 2, 3, 4, 6, and 10. Samples of all medial and lateral menisci, with attached synovium and vascular rim, from both knees were harvested and submitted for histological and/or ultrastructural examination. The results indicate that (1) at all time periods, laser cut menisci had more cell loss and matrix degradation; (2) synovial necrosis was more common in laser-treated knees; (3) the Ho:YAG laser creates three zones of damage in the meniscal fibrocartilage: a zone of fibrin and debris at the incision site, a zone of necrosis characterized by degeneration of the collagen and loss of viable cells, and a zone of thermal change characterized by collagen degeneration. The zone of thermal change, with its histological injury was thought at the time of surgery to be the viable border. The zone of thermal change may act as a barrier to delay healing, and the scalpel produced a consistently straighter cut.

Aluminum↗

Cutaneous lesions in swine after decompression: histopathology and ultrastructure.

A detailed histopathologic description of skin lesions from a porcine model of decompression sickness (DCS) is presented. Pigs were dived in a dry chamber on a variety of profiles over an 11-mo period, with a 0.1-0.6 (10-60%) incidence of cutaneous lesions. The clinical appearance of the lesions evolved from irregular, sharply demarcated areas of erythema to violaceous and, eventually, darkly mottled macules. The lesions were biopsied under deep, sedative anesthesia. Histologic abnormalities were found in 91% (20/22) of the biopsies from clinically apparent cutaneous lesions. Vascular congestion was the most common finding. Focal areas of vasculitis were noted in 45% (10/22) of the lesions. Perivascular neutrophil infiltrates, edema, and occasionally, hemorrhage were also noted. Ultrastructural abnormalities were found in all of the lesions studied. Acute inflammation affecting the dermal vasculature was the most common finding. Platelets were rarely observed aggregating within vessels. The clinical and histologic features of cutaneous lesions in pigs after decompression are compared with previous accounts in humans. The model provides a useful tool for the study of cutaneous lesions in DCS and may be a means of exploring interventions in the disease.

Animals↗

Acute neurologic decompression illness in pigs: lesions of the spinal cord and brain.

A detailed histopathologic description of central nervous system lesions from a porcine model of neurologic decompression illness is presented. Pigs were dived in a dry chamber to 200 feet of seawater for 24 min before the start of decompression. Of 120 pigs, 40 (33.3%) were functionally unaffected and 80 (66.6%) developed neurologic decompression illness; 16 died, 64 survived. Petechial hemorrhages were grossly visible in the spinal cord of 73% of the survivors, 63% of the fatalities, and 3% of the clinically unaffected pigs. The thoracic part of the cord was most commonly involved. Histologic cord lesions were found in 75 (63%) pigs: 83% of decompression illness survivors, 81% of the fatalities, and 23% of those clinically unaffected. Morphologically, hemorrhagic lesions were the most common (54%). Other common findings included spongiosis (48%), axonal swelling and loss (39%), and myelin degeneration (35%). White matter hemorrhages in the spinal cord were generally more numerous and extensive than those affecting the gray matter; however, gray matter hemorrhage was associated with increasing disease severity. Brain lesions were present in 23% of pigs and were most frequent in fatalities. Cerebellar and brain stem hemorrhages were the most common brain lesions; the molecular layer of the cerebellum appeared particularly susceptible. Pigs were chosen because of their cardiovascular and gas exchange similarities to humans. The clinical and histopathologic features of the pig model were compared with previous accounts in animals and humans; the model was judged analogous to severe human decompression illness. The finding of occult brain and cord lesions in clinically unaffected pigs is discussed. The model provides a useful tool for the study of dysbaric lesions of the central nervous system. Its noninvasive nature may facilitate the study of nervous system injury and repair processes.

Acute Disease↗

Neurological decompression illness in swine.

BACKGROUND: A porcine model of neurological decompression illness (DCI) and its treatment is described. METHODS: Pigs (wt. 16-22 kg) underwent a simulated dive to 200 feet of seawater (fsw) (612.6 kPa) for 24 min, then decompressed at 60 fsw/min-1 (183 kPa.min-1). Pigs that developed neurological DCI were sedated with diazepam, then treated by recompression on U.S. Navy Treatment Table 6. Functional outcome was assessed by treadmill running. At necropsy 24 h postdive, carcass density was measured by underwater weighing, and tissue samples including heart, spinal cord, and brain were taken for histopathological examination. RESULTS: Neurological DCI occurred in 73% of control animals and developed within 2-7 min in 50% of cases. Affected pigs had significantly earlier onset of skin DCI than unaffected pigs (means: 9.52 min vs. 17.9 min, p < 0.001). Only 16.4% of pigs made a full functional recovery after recompression treatment. Outcome at 24 h was not improved in 20 pigs randomized to receive adjunctive lidocaine infusion compared to 20 pigs that received saline alone. Following necropsy, 77% of cases had petechial hemorrhages grossly visible in the spinal cord. Multifocal, microscopic hemorrhages, predominantly of spinal cord white matter, were found in 86.6% of DCI cases. Neither weight, density, nor genetic predisposition were found to influence DCI risk. CONCLUSIONS: The model is analogous to severe, early-onset, neurological DCI in humans and allows prospective evaluation of risk reduction and treatment stratagems for this form of DCI. Many applied and basic science issues relevant to diving medicine may also be studied using the model, and adaptation to study hypobaric DCI and other clinical applications of hyperbaric oxygen is feasible.

Animals↗

Mousepox outbreak in a laboratory mouse colony.

Mousepox was diagnosed in and eradicated from a laboratory mouse colony at the Naval Medical Research Institute. The outbreak began with increased mortality in a single room; subsequently, small numbers of animals in separate cages in other rooms were involved. Signs of disease were often mild, and overall mortality was low; BALB/cByJ mice were more severely affected, and many of them died spontaneously. Conjunctivitis was the most common clinical sign of disease in addition to occasional small, crusty scabs on sparsely haired or hairless areas of skin. Necropsy findings included conjunctivitis, enlarged spleen, and pale liver. Hemorrhage into the pyloric region of the stomach and proximal portion of the small intestine was observed in experimentally infected animals. In immune competent and immune deficient mice, the most common histologic finding was multifocal to coalescing splenic necrosis; necrosis was seen less frequently in liver, lymph nodes, and Peyer's patches. Necrosis was rarely observed in ovary, vagina, uterus, colon, or lung. Splenic necrosis often involved over 50% of the examined tissue, including white and red pulp. Hepatic necrosis was evident as either large, well-demarcated areas of coagulative necrosis or as multiple, random, interlacing bands of necrosis. Intracytoplasmic eosinophilic inclusion bodies were seen in conjunctival mucosae and haired palpebra. Ectromelia virus was confirmed as the causative agent of the epizootic by electron microscopy, immunohistochemistry, animal inoculations, serologic testing, virus isolation, and polymerase chain reaction. Serologic testing was of little value in the initial stages of the outbreak, although 6 weeks later, orthopoxvirus-specific antibody was detected in colony mice by indirect fluorescent antibody and enzyme-linked immunosorbent assay procedures. The outbreak originated from injection of mice with a contaminated, commercially produced, pooled mouse serum. The most relevant concern may be the unknown location of the source of the virus and the presence of a reservoir for this virus within the United States.

Animals↗

Assessment of the histopathological lesions and chemical analysis of feral cats to the smoke from the Kuwait oil fires.

Twenty-six adult or subadult feral cats were collected from Kuwait approximately 8 months after the ignition of the Kuwait oil wells. These animals were obtained from two sources: 12 animals from Kuwait City, a relatively smoke-free area, and 14 from the city of Ahmadi, an area with heavy smoke. Animals were euthanized and a complete set of tissues consisting of all major organs was taken for histopathology. Samples of lung, liver, kidney, urine, and blood were also taken for toxicology. Histopathological lesions observed in the lung were mild accumulations of anthracotic pigment in the lungs of 17 cats. Hyperplasia of the bronchial and bronchiolar gland in 8 cats, and smooth muscle hyperplasia of bronchioles in 14 cats. Tracheal gland hyperplasia was observed in 7 cats, and minimal squamous metaplasia of the tracheal mucosa in 17 cats, Laryngeal lesions consisted of submucosal gland hyperplasia in 2 cats and squamous metaplasia of the mucosa in 5 cats. Hyperplasia of the nasal submucosal glands was observed in 6 animals. The pharyngeal mucosa as well as other organs and organ systems were normal in all cats. Atomic absorption analysis for 11 metals was performed; vanadium and nickel levels (two metals that were present in the smoke from the oil fires) are not indicative of substantial exposure to the oil fires. Based on the histopathological findings and toxicological analysis, it is felt that inhalation of air contaminated with smoke from the oil fires had little or no long-term effect on the animals examined.

Animals↗

Onchocerciasis in two dogs.

Although widely reported in cattle, horses, and other ungulates, onchocerciasis has only recently been reported in 1 dog. We report 2 additional dogs with onchocerciasis involving the palpebral conjunctiva, third palpebra, and sclera. Both dogs were evaluated because of ocular or periocular masses. Histologically, viable adult parasites were surrounded by minimal fibrosis and few macrophages. Pyogranulomas were often centered around degenerating or mineralized Onchocerca organisms. Onchocerciasis should be considered in the differential diagnosis of ocular or periocular nodules in dogs, particularly dogs from western states.

Animals↗

In vivo evaluation of the effects of gravitational force (+Gz) on over-the-wire stainless steel Greenfield inferior vena cava filter in swine.

This study was done to determine the effect of exposure to gravitational force (acceleration stress) on in vivo over-the-wire stainless steel Greenfield inferior vena cava filters. Fifteen pigs underwent venous cut down and placement of a stainless steel Greenfield filter. A 4-week observation period simulated realistic convalescence and allowed sufficient time for epithelialization. Ten pigs were exposed to acceleration stress in a centrifuge (3G run for 15 sec followed by rest until return to baseline heart rate, then a 9G run for 15 sec), with inertial loading in a head-to-tail direction (+Gz). Fluoroscopy during acceleration stress allowed assessment for filter migration. Five pigs were not exposed to acceleration stress. AP and lateral abdominal radiographs were obtained at post-filter placement, convalescence, and centrifuge exposure to determine the position and integrity of the filter. All 15 IVCs were resected and evaluated for gross or histological injury to the vessel wall. IVC filter placement was technically successful in all 15 pigs. Radiographic measurements were limited secondary to differences in pig positioning. Fluoroscopy showed no filter migration. All filters were securely attached to the vena cava by the hooks without gross evidence of perforation or hemorrhage. There were varying degrees of fibroplasia involving the hooks and tip of the filters in both the control and experimental groups. Histologically, there was evidence of prior hemorrhage at the level of the hooks, which was similar between the control and experimental groups. It is concluded that Greenfield filter position and vena caval integrity at the implantation site is unaffected by high acceleration stress.

Acceleration↗

Expression of stress proteins alpha B-crystallin, ubiquitin, and hsp27 in pallido-nigral spheroids of aged rhesus monkeys.

Ubiquitin and alpha B-crystallin belong to a class of proteins which are overexpressed in a variety of human neuropathological conditions associated with increased cellular stress. In this study we have examined the brains of aged rhesus monkeys (Macaca mulatta; n = 10, mean age: 29.7 years) using antibodies against the stress proteins ubiquitin, alpha B-crystallin, and heat shock protein 27 (hsp27). Here, we demonstrate an increased expression of ubiquitin, alpha B-crystallin, and hsp27 in spheroid bodies predominantly localized in the globus pallidus and pars reticulata of the substantia nigra. A portion of the pallido-nigral spheroids also contained ferric iron as highlighted by Perls' staining. On the basis of these findings we advance the hypothesis that expression of ubiquitin, alpha B-crystallin, and hsp27 in pallido-nigral spheroids of aged rhesus monkeys represents a stress response possibly related to increased iron-mediated oxidative stress.

Aging↗