Life-history traits of the leatherjacket Meuschenia scaber, a long-lived monacanthid.

The present study describes the age and growth of the leatherjacket Meuschenia scaber, a common Australasian monacanthid and valued by-catch of the inshore bottom trawl fishery in New Zealand. Age was determined from the sagittal otoliths of 651 individuals collected between July 2014 and March 2016 in the Hauraki Gulf of New Zealand. Otolith sections revealed alternating opaque and translucent zones and edge-type analysis demonstrated that these are deposited annually. Meuschenia scaber displayed rapid initial growth, with both males and females reaching maturity in 1-2 years and 50% of both sexes matured at 1·5 years. Maximum age differed substantially between the sexes, at 9·8 years for males and 17·1 years for females. Growth rate was similar between sexes, although males reached greater mass at age than females in the early part of the lifespan. The length-mass relationship differed significantly between the sexes, with males displaying negative allometric growth and females isometric growth. Female condition was highest in July, declined in August with the onset of spawning and showed a slight peak in January and February, immediately following the spawning season. This study substantially extends the maximum longevity recorded for monacanthids, although males had much shorter lifespans and higher mortality, than females.

Baseline donor chronic renal injury confers the same transplant survival disadvantage for DCD and DBD kidneys.

Histological assessment of baseline chronic kidney injury may discriminate kidneys that are suitable for transplantation, but has not been validated for appraisal of donation after circulatory death (DCD) kidneys. 'Time-zero' biopsies for 371 consecutive, solitary, deceased-donor kidneys transplanted at our center between 2006 and 2010 (65.5% DCD, 34.5% donation after brain death [DBD]) were reviewed and baseline chronic degenerative injury scored using Remuzzi's classification. High scores correlated with donor age and extended criteria donors (42% of donors), but the spectrum of scores was similar for DCD and DBD kidneys. Transplant outcomes for kidneys scoring from 0 to 4 were comparable (1 and 3 year graft survival 95% and 92%), but were much poorer for kidneys scoring ≥5, with 1 year graft survival only 73%, and 12.5% suffering primary nonfunction. Critically, high Remuzzi scores conferred the same survival disadvantage for DCD and DBD kidneys. On multi-variable regression analysis, time-zero biopsy score was the only independent predictor for graft survival, whereas one-year graft estimated glomerular filtration rate (eGFR) correlated with donor age and biopsy score. In conclusion, the relationship between severity of chronic kidney injury and transplant outcome is similar for DCD and DBD kidneys. Kidneys with Remuzzi scores of ≤4 can be implanted singly with acceptable results.

Beta-amyloidosis in normal aging and transmitter signaling in human temporal lobe.

Interactions between abnormal amyloid precursor protein metabolism and cholinergic dysfunction are increasingly apparent. Both of these major features of Alzheimer's disease occur in restricted loci in normal aging--a potential model for early Alzheimer type pathology. Entorhinal cortex is particularly vulnerable to beta-amyloidosis and compared with other cortical areas is remarkable for the relatively high density of nicotinic (3H-nicotine) but not other cholinergic or glutamate receptor binding. With increasing age, post-maturity, there is a persistent decline in nicotinic receptor binding in entorhinal cortex whereas muscarinic M1 and non-M1, glutamate NMDA and non-NMDA receptors are spared. Normal elderly individuals, distinguished by the absence of beta A4 immunoreactive plaques in this area, are differentiated from those with plaques by higher nicotine binding. Amongst individuals with an established history of smoking tobacco, nicotinic receptor binding and hippocampal choline acetyltransferase were elevated compared with non-smokers and preliminary evidence indicates a reduced density of cortical plaques. These findings are consistent with the hypothesis that down regulation of the nicotinic cholinergic receptor--a ligand gated calcium channel known to control the expression of neurotrophins--plays a role in the evolution of Alzheimer-type pathology.

The renal pathology of primary antiphospholipid syndrome: a distinctive form of endothelial injury.

Some features of the vascular and glomerular pathology of primary antiphospholipid syndrome (APS) are well recognized, but we describe novel glomerular ultrastructural changes that we consider to be pathognomonic of APS. Renal biopsies from eight patients with APS were examined by light and electron microscopy. All had anti-cardiolipin antibodies, and the clinical presentation ranged from fulminant multi-system disease to isolated proteinuria. By light microscopy, the hexamine silver stain showed a combination of glomerular basement membrane wrinkling and reduplication. By electron microscopy, redundant, wrinkled segments of basement membrane were accompanied by a 'new' straighter thin basement membrane adjacent to the endothelium. In two cases the presence of these antibodies was not suspected clinically, and there was no clinical history or evidence of a thrombotic microangiopathy. We describe a distinctive glomerular lesion that represents an unexplained form of endothelial injury in this syndrome.

Cyclosporin nephrotoxicity in heart and lung transplant patients.

Twenty-two patients with heart, lung or heart and lung transplants maintained on cyclosporin for periods ranging from 3 months to 10 years developed renal insufficiency which was investigated by renal biopsy. The histopathological changes were: (i) severe vascular and glomerular damage due to thrombotic microangiopathy (TM); (ii) a form of focal segmental glomerulosclerosis (FSGS); (iii) glomerular ischaemia. Rather than being separate entities, these changes appeared to represent a spectrum of pathology, some biopsies showing all three forms of glomerular injury. In all cases the glomerular changes were accompanied by arteriolar and arterial pathology, and we identified novel ultrastructural changes in the arteriolar endothelial basal lamina. Tubular atrophy was a consistent feature, the severity of which reflected the severity of the glomerular sclerosis, and which appeared to be a consequence of glomerular loss. Our findings are consistent with the nephrotoxic effects of cyclosporin being mediated chiefly via damage to preglomerular vessels and glomerular capillary endothelium. From an analysis of the clinical aspects of these cases, the effects of cyclosporin appear to be to some extent idiosyncratic, and therefore not entirely preventable, but strict monitoring of blood cyclosporin levels is essential to minimize the risk of permanent renal damage. Monitoring urinary protein in addition to plasma creatinine may detect the onset of FSGS, as proteinuria precedes creatinine elevation.

Malignant mesothelioma: a review of 35 cases with diagnosis and prognosis.

Twenty-five men and 10 women with malignant mesothelioma seen at the Austin Hospital between 1965 and 1978 were reviewed. The patients ranged in age from 34 to 79 yr. Prognosis was poor but was somewhat better for patients with epithelioid tumours than for patients with fibrous mesotheliomas and biphasic tumours. A history of occupational exposure to asbestos was obtained in the majority of patients, the latent period being from 18 to 52 yr. Ten patients had no history of asbestos exposure. The pathological diagnosis was established on tissue obtained at open biopsy in 22 cases and at post mortem in 11. Needle biopsy provided a diagnosis in only 2 cases. Cytology suggested a diagnosis of mesothelioma in 1 case. Gross pathology in general conformed with a diffuse confluent-nodular serosal tumor. A right sided preponderance was found in pleural tumours, and metastases were found rather more frequently than is usually reported. Histological features were distinctive in the majority of cases provided that sufficient material was examined. Recognition of coexisting patterns was often more helpful in making the diagnosis than any one single feature. Histochemical reactions are useful in distinguishing mesothelioma from mucin-secreting adenocarcinoma. In a majority of cases the histology and histochemistry were not characteristic and the diagnosis depended on the clinical features and the absence of another primary source of tumour.

Thorotrast-induced bilateral carcinoma of the kidney.

A case of transitional cell carcinoma in the left kidney 25 years after urinary tract investigations, and squamous cell carcinoma in the right kidney 6 years later is described. Thorotrast was identified in the kidneys and in the reticulo-endothelial system post mortem and was presumably the contrast material used for the original retrograde pyelogram. When retained in the kidneys after retrograde pyelography Thorotrast produces a characteristic radiological and histological appearance and can be identified by the spectrum of radiation which it emits. The authors believe that this report of bilateral renal carcinomas related to Thorotrast is unique.

Clonal divergence in lung cancer development is associated with allelic loss on chromosome 4.

Patients who receive curative treatment for lung cancer can develop additional lung tumors that may or may not be related to the original tumor and thus require different clinical management. If a subsequent tumor has a pattern of allele loss, revealed by allelotype analysis, overlapping that of the first tumor, it is believed to be a local recurrence or metastasis. In this case history, we present loss of heterozygosity analyses of the original primary tumor, and two second primary tumors occurring in the ipsilateral and the contra-lateral lungs. The allelotyping suggests that these tumors are all clonally related but concordance is not complete. Our interpretation is that the original primary tumor and the two new primary tumors have developed to full malignancy independently, but are clonally related, possibly via a clone of motile progenitor cells. Deletion mapping of DNA from biopsies of this patient delineated a region in 4p16 that we had previously shown to be lost in the transition from carcinoma in situ to invasive tumor. We identified a minimally deleted region encompassing six genes including two candidate tumor suppressor genes, CRMP1 a lung cancer metastasis-suppressing gene and PPP2R2C a gene for a regulatory subunit of the PP2 complex known to suppress tumorigenesis, particularly viral induced transformation.

The components of an alpha-glycerophosphate cycle and their relation to oxidative metabolism in the lens.

1. The concentration of ATP in a lens brei is maintained when the brei is incubated in oxygen with alpha-glycerophosphate. Lack of alpha-glycerophosphate or incubation in nitrogen causes the concentration to decrease. alpha-Glycerophosphate has some effect under anaerobic conditions but this is not sufficient to account for the maintenance in oxygen. 2. Manometric experiments show that alpha-glycerophosphate enhances the respiration of lens preparations. This respiration can be further increased by the addition of ADP and is abolished by cyanide and antimycin. The inference from these experiments is that a mitochondrial system able to oxidize alpha-glycerophosphate is present, i.e. the particulate half of the alpha-glycerophosphate cycle. 3. More than the calculated proportion of NADH is used when limiting amounts of dihydroxyacetone phosphate are added to lens tissue in spectrophotometric experiments. Dihydroxyacetone phosphate is therefore regenerated and an alpha-glycerophosphate cycle is operative. 4. A preparation of a particulate alpha-glycerophosphate dehydrogenase that takes up oxygen with methylene blue as electron acceptor is described. 5. Methods for obtaining mitochondria from lens are compared, and a useful extraction medium is defined. 6. Mitochondria with activities of the same order of magnitude as those obtained from liver, with alpha-glycerophosphate and glutamate as substrates, are prepared from epithelium detached from the capsule; some respiratory control is observed.

The metabolism of N-triphenylmethylmorpholine in the dog and rat.

1. Rats were given N-triphenyl[(14)C]methylmorpholine, triphenyl[(14)C]carbinol, N-triphenylmethyl[G-(3)H]morpholine or [G-(3)H]morpholine as single oral doses; the routes of excretion were examined. 2. Dogs were given single oral doses of N-triphenyl[(14)C]methylmorpholine. 3. (14)C-labelled metabolites were excreted mainly in the faeces in both rats and dogs; no (14)CO(2) was expired and less than 3% remained in the carcass and skin after 96hr. 4. (3)H-labelled metabolites were excreted rapidly in urine; part of the label was found in the expired gases and over 10% remained in the carcass and skin after 96hr. 5. Differences in excretion pattern between the sexes were noticed in rats but not in dogs. 6. N-Triphenylmethylmorpholine was rapidly hydrolysed to form triphenylcarbinol and morpholine in the stomach; morpholine was absorbed rapidly and excreted largely unchanged, though some was degraded, since some of the (3)H was found in water. 7. Triphenylcarbinol was absorbed only slowly and was oxidized to p-hydroxyphenyldiphenylcarbinol. 8. Both triphenylcarbinol and its p-hydroxy derivative were found in urine, bile and faeces in the free form and conjugated with glucuronic acid. The proportion of conjugates was higher in rat bile than in faeces. 9. Traces of o-hydroxyphenyldiphenylcarbinol and m-hydroxyphenyldiphenylcarbinol were detected as metabolites both free and conjugated.

Hypertrophic pulmonary osteoarthropathy in association with a bronchial carcinoid tumour.

A patient with hypertrophic pulmonary osteoarthropathy associated with a bronchial carcinoid tumour is described. The undoubted Kultschitsky cell origin of this tumour was confirmed on light and electron microscopic levels. The conditions known to be associated with this syndrome are reviewed.

Open lung biopsy for investigation of acute respiratory episodes in patients with HIV infection and AIDS.

BACKGROUND: Open lung biopsy (OLB) is rarely necessary for investigation of HIV positive patients with acute respiratory episodes because of the high yield from fibreoptic bronchoscopy with bronchoalveolar lavage (BAL). METHODS: A retrospective review of OLB in HIV positive patients admitted to a specialist inpatient unit with acute respiratory symptoms was carried out in order to define clinical indications, diagnostic yield, impact on management, complications and outcome. RESULTS: OLB was performed in 23 patients; 21 had undergone one or more bronchoscopies with BAL (5 also had negative results from transbronchial biopsy). Indications for OLB were: Group A, 15 patients thought clinically to have pneumocystis pneumonia but not responding to treatment; Group B, 4 patients with focal chest radiographic abnormalities; Group C, 4 patients with diffuse radiographic abnormalities and miscellaneous conditions. Preoperative PaO2 (on air) ranged from 4.4 to 14.5 (mean = 9.5) kPa. The results of OLB were in Group A 5 patients had non specific interstitial pneumonitis (NIP), 1 also had Kaposi's sarcoma, 4 had pneumocystis pneumonia (1 also had bronchiolitis obliterans organising pneumonia [BOOP]), 3 had Kaposi's sarcoma and 1 had BOOP and emphysema, 1 had pulmonary infarction and no infection and 1 had normal lung tissue. In Group B diagnoses were NIP, B cell lymphoma, occult alveolar haemorrhage and Pseudomonas aeruginosa pneumonia with BOOP; In Group C 2 patients had NIP and 2 had pneumocystis pneumonia (1 also had cytomegalovirus pneumonitis). All patients survived surgery and none required mechanical ventilation. OLB results significantly affected management; in Group A inappropriate treatment was discontinued in 11 patients found not to have pneumocystis pneumonia, and alternative therapy was begun in the 4 with pneumocystis and in Groups B and C 6 patients began specific therapy; unnecessary therapy was avoided in one and antimicrobial treatment was modified in one. CONCLUSIONS: Open lung biopsy in HIV positive patients with focal and diffuse radiographic abnormalities has a high diagnostic yield and low morbidity. This investigation should be considered in those with acute respiratory episodes and negative results from bronchoscopic investigations or who have contra-indications to this procedure.

Histologically atypical Pneumocystis carinii pneumonia.

BACKGROUND: Infection with Pneumocystis carinii typically results in a pneumonia which histologically is seen to consist of an eosinophilic foamy alveolar exudate associated with a mild plasma cell interstitial infiltrate. Special stains show that cysts of P carinii lie within the alveolar exudate. Atypical histological appearances may occasionally be seen, including a granulomatous pneumonia and diffuse alveolar damage. In these patients the clinical presentation may be atypical and results of investigations negative unless lung biopsies are performed and tissue obtained for histological examination. METHODS: The incidence and mode of presentation of histologically atypical pneumocystis pneumonia was studied in a cohort of HIV-I antibody positive patients. RESULTS: Over a 30 month period 138 patients had pneumocystis pneumonia, of whom eight (6%) had atypical histological appearances which were diagnosed (after negative bronchoalveolar lavage) by open lung biopsy in five, percutaneous biopsy in one, and at post mortem examination in two. Atypical appearances included granulomatous inflammation in four patients, "pneumocystoma" in two (one also had extrapulmonary pneumocystosis), bronchiolitis obliterans organising pneumonia in one patient, diffuse alveolar damage and subpleural cysts in one (who also had intrapulmonary cytomegalovirus infection), and extrapulmonary pneumocystosis in two patients. CONCLUSIONS: Various atypical histological appearances may be seen in pneumocystis pneumonia. Lung biopsy (either percutaneous or open) should be considered when bronchoalveolar lavage is repeatedly negative and evidence of P carinii should be sought, by use of special stains, in all lung biopsy material from HIV-I antibody positive patients.

Interstitial pneumonitis in patients infected with the human immunodeficiency virus.

BACKGROUND: A study was performed to identify the clinical, radiographic, and histopathological features of interstitial pneumonitis in patients infected with the human immunodeficiency virus. METHODS: A retrospective review was made of the case notes, chest radiographs, and histopathological results of seven HIV-1 antibody positive patients with symptomatic diffuse pulmonary disease and a pathological diagnosis of non-specific interstitial pneumonitis. RESULTS: All patients had dyspnoea, with or without cough, and chest radiographs showing diffuse infiltrates. The arterial oxygen tension ranged widely from 5.9 to 13.1 kPa. The initial clinical diagnosis was Pneumocystis carinii pneumonia in most cases. The pathological diagnosis was made by transbronchial biopsy in one case and by open lung biopsy in six cases. The interstitial pneumonitis consisted of a patchy lymphocytic infiltrate composed of B cells in focal aggregates and T cells in a more diffuse distribution. The T cell population was a mixture of CD4+ and CD8+ cells. The histological findings contrast with the more extensive infiltrate of predominantly CD8+ lymphocytes seen in HIV-associated lymphocytic interstitial pneumonitis which occurs mainly in children. The condition ran a subacute course. Three patients spontaneously improved and three improved with steroid therapy. Long term survival was less than three years, the prognosis being determined by other infective or neoplastic complications. CONCLUSIONS: Non-specific interstitial pneumonitis usually presents with an illness resembling Pneumocystis carinii pneumonia but occurs when the CD4 and total lymphocyte counts are still preserved. The pneumonitis resolves spontaneously or responds to steroids, and does not itself lead directly to the patient's death. It does, however, appear to mark a downturn in the course of HIV infection.

Diagnosis of pulmonary disease in human immunodeficiency virus infection: role of transbronchial biopsy and bronchoalveolar lavage.

The value of transbronchial biopsy and bronchoalveolar lavage was assessed in the diagnosis of pulmonary disease in patients infected with the human immunodeficiency virus (HIV). Seventy four transbronchial biopsy and 66 bronchoalveolar lavage specimens (60 paired specimens) from 80 examinations in 64 patients were reviewed. Pneumocystis carinii was the most common pathogen isolated (43 patients). Bronchoalveolar lavage was superior to transbronchial biopsy for the diagnosis of this pathogen, the sensitivities being 90% and 56%. Cytomegalovirus was identified three times by lavage and once by transbronchial biopsy. Neither method detected Kaposi's sarcoma in the one patient shown to have it by open lung biopsy. The complication rate in a concurrent study of bronchoscopy with transbronchial biopsy in 74 consecutive HIV positive patients was 22%. This study does not support the use of transbronchial biopsy in these patients.

Rapid methods for testing the efficacy of sterilization-grade filter membranes.

The validation of sterilization-grade membranes is integral to ensuring the efficient and safe use of microfiltration systems. Here validation refers to the production of sterile filtrate for sterilizing-grade membranes under challenge test conditions. Current validation methods require 48 h of culture for results to become available, which creates time delays within the manufacturing process and quality control (QC) backlogs. This work compares four methods for the production of filter challenge test data, to the desired test sensitivity, within 24 h using bioluminescent and fluorescent recombinant strains of the test organism Brevundimonas diminuta. These methods should provide a way to implement more rapid QC test regimens for filters.

Nephrotic syndrome, malignant thymoma, and myasthenia gravis. Case report and review of the literature.

We describe a patient with nephrotic syndrome due to focal-segmental glomerulosclerosis, occurring 3 years after thymectomy and myasthenia gravis. Nine other cases of nephrotic syndrome associated with thymoma and myasthenia gravis reported in the literature are reviewed. The nephrotic syndrome may be due to T cell dysfunction associated with thymoma; however, animal models suggest that genetic factors may also be involved.

The comparative metabolism of 2,6-dichlorothiobenzamide (Prefix) and 2,6-dichlorobenzonitrile in the dog and rat.

1. A single oral dose of either [(14)C]Prefix or 2,6-dichlorobenzo[(14)C]nitrile to rats is almost entirely eliminated in 4 days: 84.8-100.5% of (14)C from [(14)C]Prefix is excreted, 67.3-79.7% in the urine, and 85.8-97.2% of (14)C from 2,6-dichlorobenzo-[(14)C]nitrile is excreted, 72.3-80.7% in the urine. Only 0.37+/-0.03% of the dose of [(14)C]Prefix and 0.25+/-0.03% of the dose of 2,6-dichlorobenzo[(14)C]nitrile are present in the carcass plus viscera after removal of the gut. Rats do not show sex differences in the pattern of elimination of the respective metabolites of the two herbicides. The rates of elimination of (14)C from the two compounds in the 24hr. and 48hr. urines are not significantly different (P >0.05) from one another. 2. After oral administration to dogs, 85.9-106.1% of (14)C from [(14)C]Prefix is excreted, 66.6-80.9% in the urine, and 86.8-92.5% of (14)C from 2,6-dichlorobenzo[(14)C]nitrile is excreted, 60.0-70.1% in the urine. Dogs do not show sex differences in the pattern of eliminating the metabolites of either Prefix or 2,6-dichlorobenzonitrile. 3. Dogs and rats do not show species differences in the patterns of elimination of the two herbicides. 4. Prefix and 2,6-dichlorobenzonitrile are completely metabolized; unchanged Prefix and 2,6-dichlorobenzonitrile are absent from the urine and faeces, and from the carcasses when elimination is complete. In the hydrolysed urine of rats dosed with either [(14)C]Prefix or 2,6-dichlorobenzo[(14)C]nitrile, 2,6-dichloro-3-hydroxybenzonitrile accounts for approx. 42% of the (14)C, a further 10-11% is accounted for by 2,6-dichlorobenzamide, 2,6-dichlorobenzoic acid, 2,6-dichloro-3- and -4-hydroxybenzoic acid and 2,6-dichloro-4-hydroxybenzonitrile collectively, and 25-30% by six polar constituents, of which two are sulphur-containing amino acids. 5. In the unhydrolysed urines of rats dosed with either [(14)C]Prefix or 2,6-dichlorobenzo[(14)C]nitrile, there are present free 2,6-dichloro-3- and -4-hydroxybenzonitrile, their glucuronide conjugates, ester glucuronides of the principal aromatic acids that are present in the hydrolysed urines, and two sulphur-containing metabolites analogous to mercapturic acids or premercapturic acids. 6. Prefix is thus extensively transformed into 2,6-dichlorobenzonitrile: R.CS.NH(2)-->R.CN+H(2)S, where R=C(6)H(3)Cl(2). However, the competitive reaction: R.CS.NH(2)+H(2)O-->R.CO.NH(2)+H(2)S takes place to a very limited extent.