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Supranormal perceptual performance has been observed within the intact senses of early-deaf or blind humans and animals. For cortical areas deprived of their normal sensory input, numerous studies have shown that the lesioned modality is replaced by that of the intact sensory modalities through a process termed crossmodal plasticity. In contrast, little is known about the effects of loss of a particular sensory modality on the cortical representations of the remaining, intact sensory modalities. In the present study, an area of extrastriate visual cortex from early-deaf adult cats was examined for features of dendritic plasticity known to occur after early-deafness. Using light-microscopy of Golgi-stained pyramidal neurons from the posterolateral lateral suprasylvian (PLLS) cortex, dendritic spine density significantly increased (~19%), while spine head size was slightly but significantly decreased (~9%) following early hearing loss. Curiously, these changes were not localized to regions of the visual PLLS known to receive auditory inputs, but instead showed a broad pattern more reflective of the distribution of the area's visual features. Whereas hearing loss results in crossmodal plasticity in auditory cortices, the same peripheral lesion can also induce intramodal plasticity within representations of the intact sensory systems that may also contribute to supranormal performance., (© 2021 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

A serious fire developed in the core of a nuclear reactor at Windscale Works, Sellafield, northwest England, which led to the release of significant quantities of radioactive material into the environment during 10-11th October, 1957. In 1957, Windscale Works was operated by the United Kingdom Atomic Energy Authority (UKAEA), and on 15th October it was announced by the Chairman of the UKAEA that a Committee of Inquiry had been established under the chairmanship of Sir William Penney to conduct an investigation into the accident. The Committee sat at Windscale Works during 17-25th October, interviewed 37 people (some more than once), and examined 73 technical exhibits. The Committee reported to the Chairman of the UKAEA on 26th October. The Report of the Committee formed the technical basis of a UK Government White Paper (Cmnd. 302) published on 8th November, 1957, but the Penney Report itself was not published, and was only made public (at what is now The National Archives, TNA, Kew) in January, 1988. The original Report of the Committee of Inquiry is reproduced here from a copy of the Report supplied by TNA from TNA File AB 86/25.

The effect of carbonyl-cyanide m-chlorophenyl-hydrazone (CCCP) on intracytoplasmic membrane (ICM) assembly was examined in the purple bacterium Rhodobacter sphaeroides. CCCP blocks generation of the electrochemical proton gradient required for integral membrane protein insertion. ICM formation was induced for 8h, followed by a 4-h exposure to CCCP. Measurements of fluorescence induction/relaxation kinetics showed that CCCP caused a diminished quantum yield, a cessation in expansion of the functional absorption cross-section and a 4- to 10-fold slowing in the electron transfer turnover rate. ICM vesicles (chromatophores) and an upper-pigmented band (UPB) containing ICM growth initiation sites, were isolated and subjected to clear-native electrophoresis. Proteomic analysis of the chromatophore gel bands indicated that CCCP produced a 2.7-fold reduction in spectral counts in the preferentially assembled light-harvesting 2 (LH2) antenna, while the RC-LH1 complex, F1FO-ATPase and pyridine nucleotide transhydrogenase decreased by 1.7-1.9-fold. For 35 soluble enzymes, the ratio of 0.99 for treated/control proteins demonstrated that protein synthesis was unaffected by CCCP, suggesting that the membrane complex decline arose from the turnover of unassembled apoproteins. In the UPB fraction, an ~2-fold accumulation was observed for the preprotein translocase SecY, the SecA translocation ATPase, SecD and SecF insertion components, and chaperonins DnaJ and DnaK, consistent with the possibility that these factors, which act early in the assembly process, have accumulated in association with nascent polypeptides as stabilized assembly intermediates., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The results of a detailed structural and functional proteomic analysis of intracytoplasmic membrane (ICM) assembly in the model purple phototrophic bacterium Rhodobacter sphaeroides are reviewed in this report. Proteomics approaches have focused upon identification of membrane proteins temporally expressed during ICM development and spatially localized within the internal cell membranes, together with their structural and functional correlates. For the examination of temporal protein expression, procedures were established for the induction of ICM formation at low oxygen tension and for ICM remodeling in cells adapting to low intensity illumination, which permitted isolation by rate-zone sedimentation of ICM growth initiation sites (CM invaginations) in an upper-pigmented band (UPB), together with more mature ICM vesicles (chromatophores) as the main band. Nondenaturing clear native gel electrophoresis of the chromatophore fraction gave rise to four pigmented bands: the top and bottom bands contained the reaction center-light-harvesting 1 (RC-LH1) core complex and the LH2 peripheral antenna, respectively, while two bands of intermediate migration exhibited distinct associations of LH2 and core complexes. Proteomic analysis of the gel bands revealed developmental changes including increasing levels of LH2 polypeptides relative to those of core complexes as ICM development proceeded, as well as a large array of other associated proteins including high spectral counts for the F1FO-ATP synthase subunits, and the cytochrome bc1 complex. High counts were also observed for RSP6124, a protein of unknown function, that were correlated with increasing LH2 levels. RC-LH1-containing clear native electrophoresis gel bands from the UPB were enriched in cytoplasmic membrane (CM) markers, including electron transfer and transport proteins, as well as general membrane assembly factors (viz., preprotein translocases YidC, YajC and SecY, bacterial type 1 signal peptidase and twin arg translocation subunit TatA), thereby confirming the origin of the UPB from both peripheral respiratory membrane and sites of active CM invagination in which preferential assembly of the RC-LH1 complex occurs. Functional aspects of the photosynthetic unit assembly process were monitored by fluorescence induction/relaxation measurements of the variable fluorescence arising from LH-bacteriochlorophyll a. Slowing of the rate of RC electron transfer turnover (τQA), as assessed from the relaxation phase, was correlated with the growth of the functional absorption cross section (σ) and LH2/LH1 molar ratios. This is thought to arise from the imposition of constraints upon free diffusion of ubiquinone (UQ) redox species between the RC and cytochrome bc1 complex as the ICM bilayer becomes densely packed with LH2 rings. Such LH2 packing was confirmed in a comparison by high-resolution atomic force microscopy of ICM patches from cells grown at high and low light intensity [Adams and Hunter: Biochim Biophys Acta 2012;1817:1616-1627], in which the increasing LH2 levels form densely packed LH2-only domains, representing the light-responsive antenna complement arising under low illumination. In contrast, LH2 is initially dispersed in rows and small cluster-separating linear arrays of largely dimeric RC-LH1 core complexes, which become filled with LH2 during acclimation to reduced light intensity. In phototrophically grown cells that were transferred to oxic conditions in the dark, fluorescence induction/relaxation measurements showed that despite a growth burst independent of photosynthetic pathways, functional photosynthetic units were maintained for up to 24 h after the transition. The τQA was accelerated from ∼1 to 0.5 ms by 8 h, reflecting the decrease in LH2 levels, facilitating more rapid UQ redox species diffusion in the membrane bilayer as crowding by LH2 is overcome. Under these circumstances, UPB levels were elevated with significant increases in LH1/LH2 molar ratio. These changes indicate that vesiculation of CM growth initiation sites to form vesicular ICM was arrested under oxic conditions., (Copyright © 2013 S. Karger AG, Basel.)

Acute encephalitis is an inflammation of brain tissue that can result from activity in the central nervous system (CNS) of a number of viruses. Although the neurological and psychiatric effects of encephalitis in the acute phase of the illness are well-known (Caroff, Mann, Gliatto, Sullivan, & Campbell, 2001), larger scale studies of the pattern of neuropsychological and psychiatric impairment following recovery from the acute inflammatory phase are less apparent. This paper reports the results of neuropsychological testing with a range of standardised cognitive measures in a case series of long-term post-acute participants. Psychiatric abnormality is examined using the SCL-90-R self-report scale of distress (Derogatis, 1983). We also examined the role of emerging insight in the aetiology of depression in this population. Two clusters of cognitive dysfunction were observed, one group of primarily herpes simplex cases showing a severe generalised deficit across a number of cognitive domains and a second cluster showing a variety of more isolated disorders of executive function. Abnormally high levels of distress were reported by participants, with depression, obsessive-compulsive symptoms, interpersonal sensitivity and phobic anxiety most significantly increased. Depression was found to be least severe in those with most accurate insight into their problems. Examining the correlations between cognitive and psychiatric test results demonstrates a relationship between depression and interpersonal anxiety and specific cognitive measures. Obsessive-compulsive behaviour and phobic anxiety, however, appear to exist independently of the assessed cognitive deficits.

Background: Lung biopsies are frequently needed to diagnose diffuse interstitial lung diseases. A prospective randomized, controlled trial comparing limited thoracotomy (open lung biopsy) and thoracoscopy for lung biopsy was done., Methods: Ambulatory patients with a clinical diagnosis of diffuse interstitial lung disease were randomized to thoracoscopy or limited thoracotomy. Data on postoperative pain, narcotic requirements, operating room time, adequacy of biopsy, duration of chest tube drainage, length of hospital stay, spirometry, and complications were collected., Results: A total of 42 randomized patients underwent lung biopsy (thoracoscopy 20, thoracotomy 22). The two study groups were comparable with respect to age, gender, corticosteroid use, and preoperative spirometry. Visual analog scale pain scores were nearly identical in the two groups (p = 0.397). Total morphine dose was 50.8 +/- 27.3 mg in the thoracoscopy group and 52.5 +/- 25.6 mg in the thoracotomy group (p = 0.86). Spirometry (FEV1) values in the two groups were not significantly different on postoperative days 1, 2, 14, and 28 (p = 0.665). Duration of operation was similar in both groups (thoracoscopy 40 +/- 30 minutes, thoracotomy 37 +/- 15 minutes; p = 0.67). The thoracoscopy and thoracotomy groups had equivalent duration of chest tube drainage (thoracoscopy 38 +/- 28 hours, thoracotomy 31 +/- 26 hours; p = 0.47) and length of hospital stay (thoracoscopy 77 +/- 82 hours, thoracotomy 69 +/- 55 hours; p = 0.72). Definitive pathologic diagnoses were made in all patients., Conclusions: There is no clinical or statistical difference in outcomes for thoracoscopic and thoracotomy approaches. Both thoracoscopy and thoracotomy are acceptable procedures for diagnostic lung biopsy in diffuse interstitial lung disease.

We report a case of tracheal adenoma presenting as hemoptysis and reversible airflow obstruction in an ex-smoker. A questionable defect in the tracheal air shadow on a posteroanterior chest radiograph was shown on CT to be a pedunculated, mid-tracheal tumor. Two-stage bronchoscopic laser resection resulted in an apparently normal tracheal mucosa. Results of postresection spirometry were normal.

A 30-year-old female presented shortly after cadaveric renal transplantation with respiratory distress typical of a bacterial infection. Following initial improvement, she developed progressive respiratory failure, initially felt to be secondary to cytomegalovirus infection. Two bronchoalveolar lavages were nondiagnostic, and an open lung biopsy was performed, which revealed a pulmonary alveolar proteinosis (PAP) reaction and exogenous lipid pneumonia (ELP). The ELP was considered to be secondary to the use of marijuana, in the form of weed oil, that was smoked daily for over 10 years and stopped just before renal transplantation. This is the first description of both PAP and ELP following renal transplantation, and the first description of ELP related to smoking weed oil. Physicians should be aware of the different forms of marijuana available and of their potential medical complications.

Background: We have encountered instances where young subjects with idiopathic spontaneous pneumothorax have been needlessly referred for investigation of pulmonary hypertension because surgical pathologists have misinterpreted the significance of medial hypertrophy and intimal fibrosis of muscular pulmonary arteries in lung resection specimens., Methods: We reviewed 20 cases of idiopathic spontaneous pneumothorax and determined the prevalence and severity of medial and intimal lesions in the pulmonary arteries and pulmonary veins. We correlated the vascular changes with inflammation and fibrosis in the lung., Results: Pulmonary artery medial hypertrophy was seen in 15% of cases, pulmonary artery intimal fibrosis in 90% of cases, and pulmonary vein intimal fibrosis in 80% of cases. In 95% of cases, the lung showed some fibrosis and chronic inflammation. There was a significant positive correlation between pulmonary artery medial thickness and lung fibrosis and inflammation scores., Conclusions: Pulmonary artery medial hypertrophy and intimal fibrosis of pulmonary arteries and pulmonary veins are commonly seen in resected lung tissue from patients with idiopathic spontaneous pneumothorax. The vascular lesions are probably secondary to chronic inflammation and fibrosis in the adjacent lung. They are not clinically significant and do not represent hypertensive pulmonary vascular disease.

The unusually muscular pulmonary arteries normally present in cattle and swine residing at low altitude are associated with a rapid development of severe pulmonary hypertension when those animals are moved to high altitude. Because these species lack collateral ventilation, they appear to have an increased dependence on hypoxic vasoconstriction to maintain normal ventilation-perfusion balance, which, in turn, maintains thickened arterial walls. The only other species known to lack collateral ventilation is the coati, which, similarly, has thick-walled pulmonary arteries. We tested the hypothesis that coatis will develop severe high-altitude pulmonary hypertension by exposing six of these animals (Nasua narica) to a simulated altitude of 4,900 m for 6 wk. After the exposure, pulmonary arterial pressures were hardly elevated, right ventricular hypertrophy was minimal, there was no muscularization of pulmonary arterioles, and, most surprising of all, there was a decrease in medial thickness of muscular pulmonary arteries. These unexpected results break a consistent cross-species pattern in which animals with thick muscular pulmonary arteries at low altitude develop severe pulmonary hypertension at high altitude.

This study sought to determine if T-cell cytokine responses to mycobacterial infections in sheep were similar to those in other species and if such responses correlated with prevailing gut pathology. Lymphocytes were isolated from the blood (PBL), mesenteric lymph nodes (MLN) and ileal lamina propria (LPL) of control sheep and of sheep with clinical Johne's disease due to infection with Mycobacterium avium ssp. paratuberculosis (M.a. paratuberculosis). These animals had previously been categorised into two groups exhibiting either the 'tuberculoid' (paucibacillary) form of lesion or the 'lepromatous' (multibacillary) form. Lymphocytes were examined for their capacity, following stimulation with johnin-PPD, to release interferon-gamma (IFN-gamma) and interleukin 2 (IL-2) characteristic of the Th1 subset of MHC Class II-restricted CD4+ (helper) T-cells in other species. The expression of the two cytokines appeared related to the type of histological lesion observed. Antigen-stimulated lymphocytes from the tuberculoid group exhibited greater release of IFN-gamma and IL-2 than lymphocytes from the lepromatous group suggesting a Th1-type of response in the former in which expression of IFN-gamma by PBL showed a significant positive correlation with that expressed by MLN and LPL. Lymphocytes from animals with lepromatous lesions released lesser mycobacterium-induced IFN-gamma and IL-2 indicating a diminished role for a Th1 subset in this group of sheep. Differences in cytokine expression were much more apparent with lymphocytes which were derived from MLN.

Nineteen adult sheep diagnosed as having clinical paratuberculosis (Johne's disease) and 16 unaffected controls were examined in this study. Animals were tested for the presence of circulating antibodies of Mycobacterium avium ssp. paratuberculosis (M. a. paratuberculosis) and lymphocytes derived from the blood, mesenteric lymph nodes and intestines were examined for cell-mediated immune (CMI) responses to Johnin pure protein derivative (Johnin-PPD: J-PPD). Bacteriological examinations were carried out on faeces and tissues and any mycobacterial isolates identified as M. a. paratuberculosis (IS900+) or M. avium ssp. silvaticum (M. a. silvaticum) (IS901+) by polymerase chain reaction (PCR). Full necropsy and histopathological studies were performed and diseased animals were categorised on the basis of having a lepromatous or tuberculoid form of intestinal pathology. Unaffected control sheep were generally antibody-negative and demonstrated varying CMI responses to J-PPD. Clinically-affected animals were almost always antibody-positive with variable CMI responses. A correlation was observed between the histological lesion type in the intestine and the cellular immune response. Tuberculoid-type lesions were associated with strong CMI responses in lymphocytes derived from the peripheral blood, mesenteric lymph node and intestine, whereas lepromatous-type lesions were associated with weak CMI responses in all tissues examined.

We describe the second example of a duodenal-caval fistula in a patient with peptic ulcer disease. This condition was complicated by embolization of intestinal contents to the lung, with abundant intravascular mucin. This is the first histological documentation of intravascular mucin apart from amniotic fluid embolism. It is well known that mucin may activate coagulation. We propose that intravascular mucin activated the coagulation cascade in our patient, causing disseminated intravascular coagulation and adult respiratory distress syndrome.

An unusual case of Mycobacterium avium complex infection occurred in a young adult with no preexisting disease and no evidence of immunodeficiency. There was diffuse interstitial involvement of the lungs which suggested an active alveolitis. Diagnosis required open-lung biopsy. Restriction fragment length polymorphism analysis and multilocus enzyme electrophoresis indicated that the source of the infection was a hot tub. The infection proved to be exceptionally responsive to treatment, and there was complete resolution with a four-drug regimen.

We describe the second example of a distinctive clinicopathologic syndrome of severe pulmonary hypertension and interstitial lung disease caused by diffuse smooth muscle proliferation of the lungs (DSMPL) occurring in a 44-year-old man of normal intelligence with no cutaneous or neurological lesions. The smooth muscle proliferation involved the walls of bronchioles, alveoli, small pulmonary arteries, and pulmonary veins. DSMPL is distinct from pulmonary lymphangioleiomyomatosis and tuberous sclerosis, and does not appear to be neoplastic or reactive. The lesions are probably best regarded as multiple hamartomas or "native benign nodular smooth muscle proliferations."

The hepatopulmonary syndrome results from erythrocytes bypassing the lung without oxygenation. In addition to ventilation-perfusion mismatching, the hypoxemia may result from portapulmonary shunting, passage around alveoli through pleural and hilar blood vessels, and intrapulmonary vascular dilatations. Dilated vascular channels between arteries and veins on the pleural surface are seen more often than dilated intrapulmonary capillaries in chronic liver disease. These anastomoses appear grossly as vascular "spider nevi" on the pleura. Portal vein-to-pulmonary vein anastomoses could produce arterial hypoxemia because the deoxygenated portal venous blood can mix with oxygenated pulmonary venous blood. There is an association of esophageal varices with the hepatopulmonary syndrome and anastomoses between the portal veins and pulmonary veins have been found in both animals and humans. As portal pressures increase, the mediastinal veins enlarge, enhancing the chance that they may penetrate the pleura and drain into pulmonary veins. Direct splenic injections in patients, however, suggest that this shunt pathway is uncommon and small. Pulmonary artery injection studies have demonstrated dilated intrapulmonary vascular segments in humans and animals. Dilation of capillaries may allow a more rapid flow through the lung and the greater distance between the erythrocyte and alveolar wall may make it more difficult to oxygenate rapidly passing erythrocytes. Pulmonary capillary dilation can explain the abnormalities of the perfusion lung scan and contrast echocardiogram that portapulmonary shunting cannot. Pulmonary hypertension may occur in chronic liver disease even without arterial hypoxemia, but it is rare. The prevalence of hypertensive pulmonary vascular disease in patients with cirrhosis of the liver is less than 1%, although a higher percentage (2%) has been found when patients with portal hypertension were studied by cardiac catheterization. The hypertensive pulmonary vascular disease (pulmonary arteriopathy with plexiform lesions) that occurs in patients with liver disease appears identical to that encountered in patients with congenital cardiac shunts and unexplained (primary) pulmonary hypertension.

Collateral ventilation can participate in ventilation-perfusion regulation by shifting normoxic gas into hypoxic lung regions. In species lacking collateral pathways, such as cattle and swine, ventilation-perfusion balance must rely heavily on hypoxic vasoconstriction, which may explain why their muscular pulmonary arteries are much thicker than those of other animal species. The presence of these unusually muscular vessels in turn may account for the vigorous pressor response to acute hypoxia in these species. The only other species known to lack collateral ventilation is the coati. To determine whether coatis fit the pulmonary circulatory pattern of cattle and swine, we measured pulmonary arterial wall dimensions and pulmonary vascular responsiveness to acute airway hypoxia in 11 adult coatis. Hypoxia caused impressive pulmonary arterial hypertension [normoxia = 17 +/- 1 (SE) Torr, hypoxia = 40 +/- 2 Torr, cardiac output unchanged]. The medial thickness of muscular pulmonary arteries (50-300 microns) was 17.1 +/- 1.8% (SD) of external diameter, a thickness unprecedented in normotensive adult mammals. We conclude that coatis fit the pattern of other species lacking collateral ventilation, since they have thick-walled pulmonary arteries and a vigorous pressor response to hypoxia.

The aim of this study was to examine the effect of reduced O2 tension on the glycosylation of transferrin. Rats were placed in a hypobaric chamber (380 mmHg) that corresponded to an altitude of 5486 m above sea level for 21 days. The animals responded with marked increases in hematocrit (from 44 to 76%) and cardiac weight, and with reductions in the concentration of plasma transferrin averaging 15%. Analyses of their plasma transferrin by serial anion-exchange and lectin affinity chromatography revealed no changes in the extent of glycan branching. However, there was a moderate rise in the proportion of fucosylated transferrin molecules (fucosylation index) and a slight decrease in the transferrin fraction bearing a tetrasialylated biantennary glycan. The fucosylation index correlated positively with plasma transferrin concentrations in the test animals, but not in the controls. In contradistinction to the situation with transferrin, hypoxic rats exhibited a reduced fucosylation index of immunoglobulin G.

Ductal adenoma is a recently described benign tumour of the breast that can be mistaken for carcinoma in both frozen and paraffin sections. Such a case is presented. Fortunately a mastectomy was not performed, but the patient did undergo axillary node dissection. Surgeons and pathologists should familiarize themselves with this lesion so that patients do not have to undergo unnecessary mastectomies and axillary node dissections.

A survey was conducted to ascertain the prevalence of Fanconi syndrome in Basenjis and to determine in which geographic regions the greatest number of affected dogs resided. A thousand questionnaires were distributed nationally, and 624 (62%) were returned. Through this survey, prevalence, geographic distribution, and breeder involvement were successfully correlated with the overall association of the disease with the Basenji breed. Ten percent (96/959) of all Basenjis involved in the survey had Fanconi syndrome. Half (50%; 48/96) of the Basenjis affected were between 4 and 8 years old. Seventy-six percent (44/58) of owners of Basenjis with Fanconi syndrome were breeding their dogs, and 93% (52/56) had owned other Basenjis before the survey was conducted. Females outnumbered males (3:1) in frequency of the disease. This ratio reflected the higher breeder participation in the survey, rather than being a true gender predilection for the disease.

We measured the carotid body volume of rats treated with chronic hypoxia alone and chronic hypoxia together with a single neonatal injection of N-ethyl-N-nitrosourea (10 mg/kg). All the animals so treated showed enlargement of their carotid bodies, but no carotid body chemodectomas occurred.

We studied the effect of continuous and intermittent normoxia for 6 and 20 wk on the muscularization of pulmonary arterioles in rats with chronic hypoxic hypertension. After 4 wk in a hypobaric chamber (380 mm Hg) the proportion of small pulmonary blood vessels with 2 elastic laminae (PVTEL) was 21.57 +/- 14.86% (SD) (n = 10) compared with 3.66 +/- 1.86% in 10 untreated control animals. Recovery using continuous normoxia and intermittent normoxia 16 h/day for 6 wk caused a reduction in PVTEL to 8.45 +/- 4.09% (n = 6) and 7.16 +/- 6.96% (n = 6), respectively. Right ventricular hypertrophy (RVH) was reversed by recovery using continuous normoxia for 6 wk but was unaffected by intermittent normoxia (16 h/day). Intermittent normoxia 8 h/day for 6 wk did not reduce the PVTEL or RVH. Continuous normoxia for 20 wk reversed the muscularization of small pulmonary vessels (PVTEL, 3.86 +/- 3.57%; n = 4) and RVH. Intermittent normoxia (16 h/day) for 20 wk significantly diminished the PVTEL to 7.39 +/- 3.73% (n = 5) but did not reduce RVH. Prolonged continuous normoxia slowly reversed the pulmonary hypertension, RVH, pulmonary vascular lesions, and polycythemia induced by chronic hypoxia. Intermittent normoxia (16 h/day) diminished the pulmonary vascular lesions but not the pulmonary hypertension, RVH, and polycythemia. Intermittent normoxia (8 h/day) was ineffective.

We have studied serum and lung tissue angiotensin converting enzyme (ACE) activity in female Wistar rats with pulmonary hypertension induced by two different methods. Chronic pulmonary hypertension was produced in one group of 10 rats (CH) by confinement in a hypobaric chamber (380 mmHg) for three weeks, and in another group fo 10 rats (M) by a single subcutaneous injection of monocrotaline (60 mg/kg body weight). In these two groups of tests rats and in 20 untreated controls (C), we evaluated right ventricular mean systolic blood pressure (Prvs mmHg), right ventricular hypertrophy, and serum ACE (n mol/ml/min). In lung tissue homogenate, we measured the specific activity of ACE (n mol/mg protein/min), alkaline phosphatase (AP) (IU/mg protein) and lactic dehydrogenase (LDH) (IU/mg protein). The Prvs in groups, C, CH, and M was 25 +/- 7 SD, 41 +/- 7, and 51 +/- 5, respectively. The ratio of right ot left ventricular weight (RV/(LV + S)%) in groups, C, CH, and M was 29 +/- 4, 52 +/- 5, and 56 +/- 7, respectively. The lung tissue ACE in groups C, CH, and M was 85 +/- 11, 65 +/- 20, and 22 +/- 5, respectively. In groups CH, and M the Prvs and RV/(LV + S)% were significantly elevated above control values while lung ACE was significant decreased (p less than 0.05). There was a significant inverse relationship between lung ACE on one hand, and Prvs (r = - 0.73) and RV/(LV + S)% (r = - 0.71) on the other hand. Serum ACE and lung AP were unchanged. In group M there was a slight but significant reduction in lung LDH. Chronic pulmonary hypertension, irrespective of its method of production, is associated with decreased lung ACE. The reduction in lung ACE is inversely proportional to the severity of pulmonary hypertension and right ventricular hypertrophy.

We induced chronic pulmonary hypertension in one group of rats by exposing them to chronic hypobaric hypoxia (380 mm Hg for three weeks) and in another group by administering a single subcutaneous dose of monocrotaline (60 mg/kg body weight). Both groups of rats showed increase of the right ventricular mean systolic blood pressure and right ventricular hypertrophy. We measured the surface area of histological sections of the left or right lungs and counted all small blood vessels with an external diameter of less than 50 microns and with a definite elastic coat lying distal to respiratory bronchioles. In the 10 rats with chronic hypoxic pulmonary hypertension the mean total number of small pulmonary blood vessels was 428.8 +/- 96.9 (SD) compared with 337.8 +/- 91.9 in 10 untreated control rats. The number of small pulmonary blood vessels per mm2 of lung tissue was 4.0 +/- 1.3 in the chronically hypoxic rats compared with 3.8 +/- 1.2 in the controls. The mean total number of small pulmonary blood vessels in nine rats with monocrotaline-induced pulmonary hypertension was 396.8 +/- 61.7 compared with 384 +/- 55.4 in three control rats. The number of small pulmonary blood vessels per mm2 lung tissue was 3.3 +/- 0.6 in the rats treated with monocrotaline compared with 3.6 +/- 0.6 in the control group. We conclude that the number of small pulmonary blood vessels is not reduced in rats with pulmonary hypertension induced by chronic hypoxia or monocrotaline.

A right ventricular endomyocardial biopsy specimen from a 30-year-old male with chromic progressive external ophthalmoplegia, retinal pigmentation and complete atrioventricular block (Kearns-Sayre syndrome) was examined in the electron microscope. There was a proliferation of mitochondria between the myofibrils and beneath the sarcolemma. Many of the mitochondria showed morphologic abnormalities not previously described in this condition. There were associated accumulations of glycogen. A similarly affected female with left anterior hemiblock developed complete atrioventricular block at age 26 years, Despite the ultrastructural changes, clinically detectable myocardial disease is not a feature of Kearns-Sayre syndrome. However, intraventricular conduction defects show an unusually rapid progression to potentially fatal complete atrioventricular block and are an indication for prophylactic cardiac pacing.

The effect of continuous and intermittent normoxia on chronic hypoxic pulmonary hypertension, right ventricular hypertrophy, and polycythemia was studied in rats. After 4 wk in a hypobaric chamber (380 mmHg), the mean right ventricular blood pressure (Prv) was 29.2 +/- 1.8 (SEM) mmHg (n = 10) compared with 11.1 +/- 1.1 mmHg in 10 untreated control animals. After recovery in room air (24 h/day) for 6 wk, the Prv was significantly reduced to 21.2 +/- 3.5 mmHg (n = 6). Recovery using intermittent normoxia (8 and 16 h/day) for 6 wk did not reduce Prv. In 10 control rats, the ratio of right to left ventricular weight (RV/(LV + S) was 28.8 +/- 1.1%. After 4 wk of chronic hypoxia the RV/(LV + S) was 48.5 +/- 2.4% (n = 10). Recovery using complete normoxia for 6 wk significantly reduced the RV/(LV + S) to 32.8 +/- 1.9% (n = 6). Intermittent normoxia (8 and 16 h/day) did not reduce RV/(LV + S). Chronic hypoxia (380 mmHg) for 4 wk elevated the hematocrit from 35 to 66%. The polycythemia was reversed by recovery using continuous normoxia for 6 wk. Intermittent normoxia (8 and 16 h/day) was ineffective.

A 17-year-old boy died of severe pulmonary hypertension due to pulmonary veno-occlusive disease. The condition was diagnosed in a lung biopsy specimen and confirmed at necropsy. The lung specimen was studied by electron microscopy and immunofluorescence microscopy. The occluded pulmonary veins were lined by intact endothelial cells, beneath which was a haphazard proliferation of collagen fibrils and smooth muscle cells. The alveolar capillaries showed thickening of the endothelial cell basement membrane with an increase in the number of cytoplasmic processes of pericytes. Electron-dense deposits were located within the thickened basement membrane. These deposits were considered to represent disintegrating extravasated erythrocytes rather than immune complexes because immunofluorescence microscopy showed no immunoglobulin or complement deposition within the lung.

The reproducibility of sputum cell counts was examined and the cell counts in patients with asthma were compared with those in patients with chronic bronchitis. Three groups of subjects were studied. Sputum from eight patients with chronic asthma and with sputum production were studied to determine the reproducibility of sputum cell counts. The findings in 10 non-smokers with asthma uncomplicated by other airway disease examined at the time of an exacerbation with sputum (group 2) were compared with those from eight smokers with chronic cough and sputum but no features of asthma (group 3). Sputum plugs were selected by microscopy to ensure their origin from the lower respiratory tract. A total cell count was performed on a trypsinised suspension, and differential and metachromatic cell counts were performed on undiluted plugs. The within specimen and test-retest reproducibility of these measurements was high (reliability coefficient, R, = 0.99 and 0.89). The sputum of the asthmatic patients was characterised by eosinophilia (69%, range 46-92%) and the presence of formaldehyde blockable metachromatic cells (1.5%, range 0.6-2.8%). In comparison, the sputum of the patients with chronic bronchitis had few eosinophils (0.5%) or metachromatic cells (0.14%); the dominant cell type was the macrophage (83%). It is concluded that sputum cell counts are reproducible in the short term, the inflammation of asthma is characterised by eosinophilia and metachromatic cells in sputum, and sputum may provide a useful source of cells for investigating the cellular characteristics of airway inflammation.

We have investigated two cases of chronic eosinophilic pneumonia using the electron microscope. The alveolar septa were thickened due to edema and an infiltrate of numerous mononuclear cells and eosinophils, with a few lymphocytes and occasional plasma cells. Macrophages were often located close to eosinophils and extracellular eosinophilic granules. Occasional eosinophilic granules were observed in the cytoplasm of mononuclear cells. The most striking finding was the presence of distinctive elongated, narrow, tubular inclusions in the cytoplasm of several of the mononuclear cells. These inclusions presented complex curved profiles which sometimes terminated in small, dilated, dense vesicles. Some of the narrow tubular sections of the inclusions presented a pentalaminar structure. Elsewhere, the tubular structures showed localized globular dilatations which contained granular material. Elongated strands of electron-dense material, identical to that forming the intracytoplasmic inclusions, were also located extracellularly, between adjacent mononuclear cells and between mononuclear cells and eosinophils. These inclusions are considered to be the product of phagocytosis of cellular debris and to be related to phagolysosomes rather than to Birbeck granules.

The lung is a target in several models of environmentally induced injury and is also a common site for the growth of metastases from circulating cancer cells. In these experiments, we have tested the hypothesis that pulmonary damage can facilitate the metastasis of cancer to the lung. We have studied the effect of monocrotaline-induced lung injury on the retention and metastasis of intravenously injected Walker carcinosarcoma 256 cells in the lung and the effect of this injury on spontaneous metastasis in animals with intramuscular tumor transplants. Female Wistar rats were given a single subcutaneous injection of monocrotaline (60 mg/kg). The degree of lung injury after monocrotaline was assessed by bronchoalveolar lavage, by histological and ultrastructural examination, and by measurement of right ventricular hypertrophy. To assess the effects of monocrotaline on metastasis, animals were injected iv with 2 X 10(7) [125I]iododeoxyuridine-labeled or unlabeled Walker 256 carcinosarcoma cells at various periods of time (1 day to 20 days) after monocrotaline. The retention of labeled cells was determined by gamma counts of lungs 24 hr after injection. There was a direct correlation between the severity of lung injury and the number of cancer cells retained in the lung 24 hr after injection. Metastasis was quantified by morphometric analysis of histologic sections prepared from lungs 1 week after an injection of unlabeled cells. The median area of lung involved by tumor after iv injection was 39% for rats injected with cancer cells 10 days after monocrotaline vs 3% for controls. In studies on spontaneous metastasis, rats were given an intramuscular injection of Walker 256 cells 5 days after monocrotaline and metastasis was quantified by morphometry 7 days after tumor transplantation. The median tumor burden of animals pretreated with monocrotaline was 37% vs 8% for controls. We conclude that lung injury initiated by monocrotaline can facilitate the spread of the rat Walker 256 carcinosarcoma.

We studied the ultrastructure of the carotid body of three normal rats and three rats living in a hypobaric chamber at a pressure of 460 mm Hg for 27, 28 and 35 days respectively. The type I cells of the carotid bodies of our hypoxic rats were enlarged due to an increase in the volume of their cytoplasm. Many of their dense core vesicles were vacuolated and the core was displaced eccentrically to become adherent to the limiting membrane of the vesicle. The concentration and distribution of dense core vesicles remained unaltered and there were no obvious changes in the mitochondria, ribosomes or Golgi apparatus. There was pronounced capillary dilatation in the carotid bodies of all three rats exposed to chronic hypoxia. This change was accompanied by attenuation of capillary endothelial cells and increased frequency of endothelial fenestrations. There were no structural changes in the type II cells.

The ratio of right to left ventricular weight (0.3), and the ratio of the medial thickness of the pulmonary trunk to that of the aorta (0.4 to 0.7) are similar in humans and other mammals for which data are available. There are interspecies differences in quantity and arrangement of collagen, smooth muscle, and elastic tissue in the pulmonary trunk. The medial thickness of muscular pulmonary arteries is similar in man, baboon, ferret, goat, llama, and monkey. In most other mammals these vessels are more muscular than those in humans. The goat is similar to man because the muscular pulmonary arteries terminate at an external diameter of 100 microns. In most other mammals, smooth muscle is present in much smaller pulmonary arterial vessels. There is pronounced interspecies variation in the course and structure of the pulmonary veins. The cat, civet, dog, ferret, fox, goat, horse, monkey, and rabbit have pulmonary veins with thin fibrous walls such as occur in humans. However, the pulmonary veins are muscular in the cow, guinea pig, llama, pig, and rat.

We have studied the role of 5-hydroxytryptamine (5-HT) in monocrotaline pulmonary hypertension and chronic hypoxic pulmonary hypertension in rats using p-chlorophenylalanine (PCPA) which inhibits 5-HT synthesis. We measured right ventricular mean systolic pressure (Prvs), right ventricular hypertrophy, medial thickness of muscular pulmonary arteries, and muscularization of pulmonary arterioles 17 days after a single dose of monocrotaline (60 mg/kg) and after 26 days of chronic hypobaric hypoxia (380 mm Hg). In monocrotaline pulmonary hypertension, pretreatment with PCPA (500 mg/kg) was associated with significant reductions (p less than 0.05) in Prvs (29%), right ventricular hypertrophy (33%), and medial thickness of muscular pulmonary arteries (14%). In chronic hypoxic pulmonary hypertension, pretreatment with PCPA was associated with significant reductions in Prvs (20%), right ventricular hypertrophy (28%), medial thickness of muscular pulmonary arteries (14%), and muscularization of pulmonary arterioles (47%). 5-HT may play a role in the development of monocrotaline pulmonary hypertension and chronic hypoxic pulmonary hypertension in rats.