Marked Pathological Changes Research Articles

Characterisation of avian adenoviruses associated with inclusion body hepatitis

Eleven avian adenoviruses were isolated in monolayer cultures of specific pathogen free chicken kidney cells which were inoculated with suspensions of liver, intestine or bursa obtained from 15 broiler flocks experiencing outbreaks of inclusion body hepatitis (10 isolates) and from five unaffected flocks (one isolate). Of the 11 isolates obtained, nine were identified by virus neutralisation tests as serotype 8, one as serotype 1 and one as serotype 12. Adeno-associated viruses were only observed in combination with adenoviral particles of the serotype 12 isolate which was derived from a relatively mild outbreak of inclusion body hepatitis. Only the serotype 1 isolate, obtained from the unaffected broiler flock, consistently caused the death of embryos with marked pathological changes. All of the isolates produced basophilic intranuclear inclusion bodies surrounded by clear halos in chicken kidney cell cultures. DNA preparations, obtained from six strains of serotype 8 avian adenovirus (two New Zealand isolates, three Australian isolates and the reference strain HVI) after digestion with the restriction enzymes EcoRI and BamHI, gave electrophoretic patterns showing the New Zealand isolates to be similar to one another and to strain HVI, but quite distinct from the Australian isolates.

Distribution and Biological Effects of Inhaled 239 Pu(NO 3 ) 4 in Cynomolgus Monkeys

Twenty male cynomolgus monkeys were exposed by inhalation either to an aerosol of 239Pu(NO3)4 to produce projected initial lung burdens of either 40, 10, or 4 kBq or to a carrier aerosol as a control. Animals died or were sacrificed at 0.01, 1, 3, 6, 12, 24, 40, and 99 months after inhalation, and the distribution and biological effects of the 239Pu were determined. The 239Pu cleared efficiently from the lungs so that less than 0.05 kBq remained at 99 months after exposure to 40 kBq. Total skeletal 239Pu activity was nearly constant after the first year, but the fraction of the body burden in skeleton at sacrifice increased with time up to 99 months because of clearance from other organs. Plutonium in the liver increased to a peak at 1 year and then decreased to about 10% of the peak value at 99 months. Plutonium in the testes was localized in the interstitial tissue with only 0.01 to 0.002% of the projected lung burden remaining in testes at 99 months after inhalation. Three animals exposed to 40 kBq of 239Pu died of radiation-related pulmonary pneumonitis and fibrosis. A primary papillary adenocarcinoma of the lung was identified in one animal exposed to 40 kBq initial lung burden and sacrificed 99 months after inhalation. The frequency of chromosome aberrations in blood lymphocytes was significantly elevated only in monkeys with projected deposits of 40 kBq of 239Pu. There was no change in aberration frequency in other exposure groups as a function of inhaled activity, time after exposure, or calculated total dose to the lungs. Only in monkeys that had marked radiation-induced pathological changes in the lung did the frequency of chromosome-type aberrations increase significantly, to a value about twice the control level. In cynomolgus monkeys, chromosome aberration frequency in blood lymphocytes is not a good indicator of radiation dose or damage from inhaled soluble plutonium.

Cardiotoxicity and Hypertension in Rats After Oral Lead Exposure

The rats were exposed to lead (0.25, 0.5 and 1.0 per cent lead acetate through drinking water) for 90 days to study its effect on some physiological and morphological parameters of the cardiovascular system. Blood lead levels increased in a dose dependent manner but heart tissue showed rise at only two higher doses in exposed animals. The two higher doses of lead resulted in an increased arterial blood pressure and calcium influx in atrial trabeculae and papillary muscles. No marked pathological or histochemical changes were observed in heart tissue excepting congestion and slightly reduced activity of succinic dehydrogenase in the highest dosed group. It was concluded that lead exposure through drinking water may produce increased arterial blood pressure and minor changes in the myocardium. Whether these changes are mediated through the effect of lead on the calcium transport needs further investigation.

Introduction to Radiosurgery

Although radiosurgery treatments began more than 30 years ago and thousands of patients have been treated, the role of radiosurgery in the treatment of intracranial lesions is continuing to evolve. For AVM several groups have reported favorable angiographic response rates. Further information, however, is needed to establish the relationship between this objective measure of response and the risk of subsequent hemorrhage. Ideally this relationship might be established through randomized trials. For ethical reasons, however, such trials are unlikely to be undertaken. Although radiosurgery may finally prove useful in the treatment of lesions other than AVM, currently available retrospective data do not allow firm conclusions in most cases. Various techniques can be used to deposit the dose accurately in a predetermined intracranial volume. Nonetheless, it frequently is difficult to define the three-dimensional configuration of the volume requiring treatment accurately. This difficulty is independent of the radiosurgical technique used and, together with dose prescription and patient selection, is probably of greater importance than possible differences in dose distribution produced by different systems. Because many patients will have radiosurgery in nontrial clinical settings, it is important that future reports provide sufficient information to allow meaningful interpretation. At minimum, reports must contain an accounting of all patients treated, including number followed and number lost to follow-up evaluation or otherwise lacking repeat radiologic studies or clinical evaluation. (The statement that 1000 patients were treated is not useful in the absence of this accounting and may cast doubt on reported results.) Beyond accounting it is helpful if reports provide (1) information on dimensions and intracranial location of lesions treated and correlation with dose and outcome, (2) quantitative information on dose prescribed, including minimum and maximum dose to the target, especially when multiple isocenters are used (when isodose contours from individual isocenters must be summed), (3) detailed information on patients developing complications (in what ways did their presentation or treatment differ from that of other patients?), and (4) thorough data analysis using modern statistical techniques. The number of radiosurgery facilities is increasing rapidly. Whether the number of patients treated in each facility will continue to rise each year as more new facilities are open is conjectural and will depend on the evolution of indications for radiosurgery and on the evolution of referral patterns as techniques, facilities, and results become established.

Effect of Corticosteroids on Diaphragm Function and Biochemistry in the Rabbit

The effects of corticosteroid administration for 2 weeks on diaphragm histology, biochemistry, and function were assessed in the rabbit at rest and during inspiratory loading to respiratory failure, and compared to the extensor digitorum longus and untreated control animals. There were marked pathologic changes in the diaphragm after corticosteroid administration and significant alterations in diaphragm glycogen level (118.7 +/- 2.8 versus 56.2 +/- 1.0 mmol/kg wet weight, p less than 0.01) and lactate level (5.3 +/- 0.3 versus 3.5 +/- 0.4 mmol/kg wet weight, p less than 0.01) with only minimal changes in the skeletal muscle. Although respiratory muscle endurance in the control group increased from 142 +/- 17 min at baseline to 155 +/- 20 at Week 1 and 183 +/- 13 at Week 2 (p less than 0.05), it fell progressively from 135 +/- 19 min at baseline to 99 +/- 5 at Week 1 and 88 +/- 9 at Week 2 (p less than 0.01) in the corticosteroid-treated animals. On the other hand, there was no significant change in resting Pdimax after corticosteroid administration. In addition, there was no significant change in Pdimax, Pdi/Edi ratio, or glycogen level at the point of respiratory failure, but diaphragm lactate levels were increased (8.5 +/- 0.8 versus 5.3 +/- 0.3, p less than 0.05). When variable degrees of diaphragm dysfunction were induced by phrenic nerve pacing and/or thoracoabdominal binding, the degree of biochemical change associated with diaphragm dysfunction was significantly greater in corticosteroid-treated animals. We conclude that corticosteroid administration in the rabbit alters diaphragm histopathology and biochemistry as well as respiratory muscle endurance, but not strength.(ABSTRACT TRUNCATED AT 250 WORDS)

Lead induced testicular hypersensitivity in stressed rats

Rats were immobilized for 2 h and treated i.p. with lead Pb2+ (8 mg/kg/day) for 45 d to investigate the testicular effects of lead on rats kept under immobilization stress. Marked alteration in SDH. G6PDH activity, cholesterol and ascorbic acid contents and reduced sperm counts associated with marked pathological changes in the testis of rats were observed after combined treatment with lead and immobilization stress in comparison to either alone. An increase in the disturbances of testicular androgen synthesis seems to be responsible for enhanced testicular injury in lead induced stressed rats.

Morphological and Functional Changes in the Rat Heart after X Irradiation: Strain Differences

The hearts of mature male rats of the Wistar and Sprague-Dawley strains were locally irradiated with single doses of 17.5 and 20.0 Gy of X rays, respectively. These two dose levels had previously been shown to result in a comparable latent period between irradiation and the death of rats of these two strains from cardiac failure. Morphological changes in the myocardium and modifications in cardiac function were assessed in the animals at 28, 70, and 100 days after irradiation. The first radiation-induced change which was observed in the myocardium was a rapid decline in capillary density and a loss of alkaline phosphatase activity by the capillary endothelial cells. The capillary density was reduced to approximately 50% of that of unirradiated control values at 28 days and to approximately 40% of the control values between 70 and 100 days after irradiation. The loss of enzyme activity was also detected at 28 days. Examination of histological sections showed an increase by 70 days in the areas with negative enzyme activity up to approximately 70% of the myocardium. The reduction in capillary density and the loss of enzyme activity occurred before any marked pathological changes were seen in the myocardium. The pathological lesions seen in the myocardium at 100 days after irradiation were qualitatively and quantitatively the same in the two strains of rat. Measurements of cardiac output in Sprague-Dawley rats showed a gradual decline in output after irradiation; however, measurements in Wistar rats showed a progressive increase in cardiac output over the same period of time. It was shown by rubidium extraction that there was an increase in the percentage of the total cardiac output distributed to the ventricular muscle of Sprague-Dawley rats, while similar measurements in Wistar rats showed no significant change. In spite of the marked strain differences observed in cardiac output and rubidium extraction, blood perfusion per gram of ventricular muscle was apparently not modified in both strains of rat after irradiation. These findings indicated that the correlation between morphological effects after irradiation and the functional expression of damage is highly complex.

Purification of an antitrypanosomal factor fromPseudomonas fluorescens by high-pressure liquid chromatography

Studies on the purification of an antitrypanosomal factor (ATF-II) obtained fromPseudomonas fluorescens disclosed that high-pressure liquid chromatography (HPLC) with a Rad-pak μporasil (10 μ silica) column and a GPC-60 A column was an efficient procedure for the separation of the active components. Extraction of the factor with absolute ethanol prior to elution significantly enhanced the lytic activity of the HPLC eluates, as shown by marked pathologic changes followed by lysis in bioassays performed withTrypanosoma equiperdum. HPLC provided an increase of purification 30 times that obtained with gel filtration of the crude bacterial product. The lipopolysaccharide content of the purified fractions was markedly reduced and indicated an additional advantage for further in vivo tests in experimental infections withT. cruzi.

Histologic changes in the guinea pig gastrointestinal tract following 1 weeks' administration of chlorpromazine, haloperidol or atropine.

A comparison was made between the toxic effects of chronic chlorpromazine, haloperidol or atropine on the guinea pig intestinal tract. Chlorpromazine, administered at a dose of 30 mg/kg/day, IP for 7 days, produced marked pathologic changes in the guinea pig cecum, consisting of inflammation, edema and hemorrhage. None of these effects were noted when haloperidol, 2 or 10 mg/kg/day or atropine 30 mg/kg/day were similarly administered. Similar toxic effects may occur in humans on long-term chlorpromazine or other phenothiazine therapy, thereby accounting for the paralytic ileus observed with these drugs.

Endotoxin permeability through the round window.

The permeability of the round window membrane to Salmonella typhimurium derived endotoxin was examined using a total of 17 chinchillas. One mg of endotoxin was instilled into the tympanic cavity via the superior bulla. Endotoxin activity in middle ear effusions (MEEs), perilymph (both inoculated and non-inoculated side), and sera was determined by Limulus lysate assay after 12, 24, 48, 72, and 120 h following endotoxin instillation. Endotoxin was detected in perilymph on the inoculated side by 12 h after endotoxin instillation and persisted for 5 days during the present measurement period. Endotoxin level peaked at 24-48 h post-instillation, and steadily declined afterwards. This result suggests that the maximum penetration occurred during the active inflammatory stage. Histologic investigation revealed marked pathological changes in the inner ear, including bleeding and inflammatory cell recruitment, mostly in the perilymphatic spaces (e.g. scalae tympani and vestibuli, spiral ligament), strial swelling, and sensory cell degeneration. These results suggest that endotoxin, when introduced into the middle ear, can permeate through the round window membrane and can cause inner ear tissue damage in this animal model.

One hundred percent oxygen lung injury in adult baboons.

Healthy adult baboons exposed to 100% oxygen for 5 to 7 days maintained on continuous mechanical ventilation develop severe bilateral noncardiogenic pulmonary edema that resembles in many aspects the human adult respiratory distress syndrome (ARDS). In the present study, we evaluated the effects of hyperoxia for 5 to 6 days in 8 baboons to compare changes in abnormalities in bronchoalveolar lavage fluid (BALF) biochemical markers, hemodynamic measurements, and pulmonary function tests in order to find early predictors of lung injury. All animals had bilateral alveolar infiltrates, severe hypoxemia, and progressive deterioration of pulmonary function tests. Diffuse alveolar damage and mild-moderate pneumonias were found and were associated with low-grade bacterial infection. Total lung capacity, diffusing capacity for carbon monoxide, pulmonary static compliance, and oxygenation were significantly impaired after Day 5; BALF proteins, elastase, and total polymorphonuclear leukocytes increased significantly at least 24 h before (Day 4) any abnormalities in chest radiographs, pulmonary function tests, and hemodynamic measurements were detected. We conclude that exposure to 100% oxygen in this model causes marked gas exchange, hemodynamic, biochemical, cytologic, radiographic, and pathologic changes similar to those noted in patients with ARDS. Bronchoalveolar lavage abnormalities precede hemodynamic and gas exchange abnormalities.

Hepatotoxicity of gossypol in rats

Gossypol acetic acid (GAA) at the dosage of 30 mg/kg daily for 2 weeks could prolong the sleeping time of pentobarbital, increase the SGPT level, decrease the liver concentration of cytochrome P-450 and GSH content, inhibit the activity of cytochrome C reductase and aminopyrine- N-demethylase, but was without effect on cytochrome b 5 and aniline hydroxylase. At a smaller daily dosage (15 mg/kg for 4 weeks), GAA could induce the rise of SGPT level and GSH content without affecting the liver metabolizing enzymes. GAA at both dosages could induce marked pathological changes of liver cells in treated rats, such as vacuolation of mitochondria, dilation of endoplasmic reticulum and widening of perinuclear space as well as proliferation of collagen fibers in Disse's spaces. GAA could induce the formation of O 2 and H 2O 2 and could inhibit Ca 2 sequestration in rat liver microsomes in vitro. ¦C 14¦-gossypol could bind to microsomal protein irreversibly either in the presence or absence of NADPH. It may be concluded that GAA is capable of causing damage to liver cells.

Myelin changes in leprous neuropathy.

Myelin changes were observed in fibres of nerves from cases of leprosy. The myelin had a 'loosened' appearance caused by increased and irregular separation of the intraperiod line. 'Loosening' might affect all, or only some, of the lamellae forming a myelin sheath. There was a patchy distribution of fibres with abnormal myelin, and they were seen only in nerves showing other marked pathological changes including the presence of oedema. The appearances are suggestive of intramyelinic oedema which may be related to the presence of endoneurial oedema.

A histopathological study on juvenile colorcarp, Cyprinus carpio, showing edema.

In 1974, from June to July, a disease which was accompanied by a considerably high mortality occurred among juvenile colorcarp, Cyprinus carpio, at many farms in Niigata Pref., Japan. The outbreak of the disease has been observed in the same season every year since then. In most cases, a large number of fish died within a few days after onset of the disease. The characteristic symptom was swelling due to edema of the fish body. The purpose of the present study is to obtain the histopathological findings of the disease by light and electron microscopic observation. It was progressive change which induced club-shape transformation of gill lamellae by proliferation and thickening of epithelial cells of the secondary gill lamellae. The club-shape transformation began at the tip of the gill lamellae, gradually extends downward to spread all over the gill lamellae. As the degeneration proceeded, gill lamella-adhesions also began to occur. At this stage, the capillary cavities in secondary gill lamellae were almost occluded. In the gill filaments with marked pathological change electron microscopic observation revealed many virus-like particles in the epithelial cells of thickened secondary gill lamellae of diseased fish. The particle was about 250-280 nm in diameter and the profile was mulberry-like with an envelope. These morphological features suggest that this virus may be a member of the poxvirus group.

Vacuolar myelopathy pathologically resembling subacute combined degeneration in patients with the acquired immunodeficiency syndrome.

Twenty of 89 consecutive patients with the acquired immunodeficiency syndrome (AIDS) in whom autopsies were performed over a 3 1/2-year period had a vacuolar myelopathy that was most severe in the lateral and posterior columns of the thoracic cord. Light and electron microscopy showed that vacuoles were surrounded by a thin myelin sheath and appeared to arise from swelling within myelin sheaths. Signs and symptoms referable to the spinal-cord lesions, including paraparesis, often accompanied by spasticity or ataxia (or both), were present in all five patients with marked pathological changes, in five of seven patients with moderate changes, and in two of eight patients with mild changes. Fourteen patients were demented. The clinical presentation was sufficiently distinctive to provide a guide for antemortem diagnosis. Possible causes of the vacuolar changes include uncharacterized viral infection or a metabolic derangement related to selective nutritional deficiency.

Synthesis and Evaluation of Some Alkoxy-, Chloro-, and Acyloxy-Conjugated Styryl Ketones Against P-388 Lymphocytic Leukemia and an Examination of the Metabolism and Toxicological Effects of l-(m-Ethoxymethyloxyphenyl)-l-nonen-3-one in Rats

A number of analogs of a new antineoplastic agent, l-(m-ethoxymethyloxyphenyl)-l-nonen-3-one (IIIa) were prepared and evaluated against murine P-388 lymphocytic leukemia. Metabolic studies of IlIa in rats showed that it was sequestered rapidly to the brain and hence probably to other adipose tissue, which may account for the absence of IlIa and metabolites in urine and feces. A detailed toxicological evaluation of IlIa in rats showed marked pathological changes principally in the liver and spleen as a result of erythrophagocytosis from bleeding into the abdomen.

Noradrenaline levels and morphologic alterations of myocardium in experimental protein-calorie malnutrition.

Experimental protein-calorie malnutrition was produced in rats by giving them a low-protein diet for 6 weeks. Control animals were fed a high-protein diet. The deficient rats showed severe restriction of body weight gain, fatty liver and hypoproteinaemia. In addition the present study demonstrates that the experimentally induced protein-calorie malnutrition brings about marked pathological changes and increased catecholamine levels in the hearts of rats. Based on this demonstration, and considering the synchronism of morphological and biochemical data, we postulate that the nutritional stress to the heart raises the myocardium noradrenaline concentration and the continued exposure to high levels of catecholamines may play a role in the development of cardiac changes in protein-energy malnutrition.

Biochemical effects of pure isomers of hexachlorobiphenyl: Fatty livers and cell structure

The effects of a single oral dose (50 mg/kg body wt.) of 3,4,5,3',4',5'-hexachlorobiphenyl (HCB), 2,4,5,2',4',5'-HCB or 2,3,5,2',3',5'-HCB for a period of 72 h have been studied in the male rat. Only 3,4,5,3',4',5'-HCB caused necrosis of thymocytes. 3,4,5,3',4',5'-HCB caused marked pathological changes in the liver with less marked effects being caused by 2,4,5,2',4',5'-HCB and 2,3,5,2',3',5'-HCB. Total lipid content was increased by all the isomers studied, but 3,4,5,3',4',5'-HCB had more pronounced effect on total lipid content. Lipid accumulation was pericentral in the livers obtained from rats treated with 3,4,5,3',4',5'-HCB, but midzonal in the liver obtained from the rats treated with the other two isomers. Analysis of various lipid fractions showed that triacylglycerols were increased seven-fold only by 3,4,5,3',4',5'-HCB, while phospholipids were increased slightly by 2,4,5,2',4',5'-HCB or 2,3,5,2',3',5'-HCB. Only 3,4,5,3',4',5'-HCB increased the level of total and esterified cholesterol. These results show that the fatty livers caused by 3,4,5,3',4',5'-HCB were qualitatively and quantitatively different from those caused by the other two isomers at the same dose. For the first time a hexachlorobiphenyl unchlorinated in the para position, 2,3,5,2',3',5'-HCB has been shown to be a specific inducer of cytochrome P-450. The effects of 2,3,5,2',3',5'-HCB on cell structure and phospholipid content were quantitatively similar to those caused by 2,4,5,2',4',5'-HCB. Thus, chlorination at para (4,4') positions in chlorobiphenyls is not necessarily required for biological activity. It is hypothesized that net stereoelectronic properties of the isomers or resistance to metabolism may be the underlying factor in determining structure-activity relationships.

Alcohol ingestion-induced changes in the human rectal mucosa: light and electron microscopic studies.

Histologic and ultrastructural examination of specimens of rectal mucosa from 11 patients who had recently consumed excessive quantities of alcohol revealed marked pathologic changes. Goblet cells were decreased and a dense mononuclear cell infiltrate was seen on light microscopic study. Electron microscopy revealed swollen, distorted mitochondria and dilated and vesicular endoplasmic reticulum. These abnormalities disappeared after two weeks' abstinence. It is suggested that disordered organelle structure and function might contribute to the diarrhea frequently observed following excessive alcohol intake.

Swimbladder and skeletal deformations in hatchery bred Spams aurata

Among hatchery bred Sparus aurata, 5.4% of the offspring of a single parent pair showed severe skeletal deformations coupled with marked growth retardation and pathological changes in the swimbladder. This resulted from extreme proliferation, then hypertrophy, of the cuboidal epithelial cells of the gas gland and proliferation of the rete mirabile. This caused almost complete congestion of the swimbladder air space. The nature of the pathological changes in the swimbladder and the possibility of hereditary origin for both the skeletal and swimbladder deformations are discussed.