Biomedical subjects
Publications and source records attributed to J Eng.
A rare case of metastatic malignant melanoma of the esophagus 11 years after wide excision of a cutaneous malignant melanoma is presented and the relevant literature reviewed. Symptomatic esophageal metastasis is unusual in malignant melanoma. Although the eventual outlook is poor in such cases, worthwhile palliation can be achieved by prompt diagnosis and treatment.
To reduce the risk of damage to the anterior surface of the right ventricle after resternotomy, it has been recommended that the pericardium be closed with a patch after open heart operations. We have examined 4 patients undergoing resternotomy for the third time 3 to 8 years after bovine pericardium valve replacement. On each occasion the pericardium was closed with a patch of bovine pericardium. In all cases, the patch was frozen to the inner aspect of the sternum, increasing the difficulty of resternotomy. Histological examinations of the patches confirmed dense fibrous connective tissue, patchy calcification, and foreign body giant cell reaction. Bovine pericardium appears to increase the difficulty of repeat cardiac operations. We recommend its use be discontinued.
Monomeric n-butyl-2-cyanoacrylate was used in 25 patients undergoing pulmonary resections to strengthen the bronchial stump after pneumonectomy (n = 11) and to aid bronchial (n = 13) and tracheal anastomosis (n = 1) after sleeve resections. Neither group had any incidence of bronchopleural fistula. Bronchial anastomosis was accomplished in patients who underwent sleeve resection, reducing the number of sutures required to four apposing sutures, with the tissue adhesive ensuring an airtight closure. There was no incidence of bronchial stenosis. The efficacy of n-butyl-2-cyanoacrylate in preventing fistula formation after bronchial resections makes it an ideal agent in pulmonary surgery. Its use obviated the use of pedicled pleural flap, thus ensuring pleural integrity for extrapleural continuous intercostal nerve blockade for postoperative analgesia.
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Nicotinamide adenine dinucleotide (NADH) plays a critical role in oxidative phosphorylation as the primary source of reducing equivalents to the respiratory chain. Using a modified fluorescence microscope, we have obtained spectra and images of the blue autofluorescence from single rat cardiac myocytes. The optical setup permitted rapid acquisition of fluorescence emission spectra (390-595 nm) or intensified digital video images of individual myocytes. The spectra showed a broad fluorescence centered at 447 +/- 0.2 nm, consistent with mitochondrial NADH. Addition of cyanide resulted in a 100 +/- 10% increase in fluorescence, while the uncoupler FCCP resulted in a 82 +/- 4% decrease. These two transitions were consistent with mitochondrial NADH and implied that the myocytes were 44 +/- 6% reduced under the resting control conditions. Intracellular fluorescent structures were observed that correlated with the distribution of a mitochondrial selective fluorescent probe (DASPMI), the mitochondrial distribution seen in published electron micrographs, and a metabolic digital subtraction image of the cyanide fluorescence transition. These data are consistent with the notion that the blue autofluorescence of rat cardiac myocytes originates from mitochondrial NADH.
The rat has been a useful model for studying neuronal and metabolic abnormalities associated with fetal and neonatal hypothyroidism produced by treatment of the mother with antithyroid medication. The neonates are then maintained on this medication via the mother's milk until weaning and subsequently through the drinking water. We have determined the concentrations and contents of immunoreactive cholecystokinin (CCK) and vasoactive intestinal peptide (VIP) in the brain and gut of groups of rats exposed to antithyroid medication from day 16 of gestation. The neonates were sacrificed at 2, 4, 8 and 12 weeks. Compared to controls total body weight was greatly reduced in methimazole (MMI)-treated rats, all of whom were hypothyroid as evidenced by marked reduction of T4 and increase in TSH. Discontinuation of MMI-treatment after 8 weeks resulted in normalization of T4 and TSH and a dramatic weight gain but at 12 weeks the brain weights of the MMI-treated rats were reduced by 17% and the brain contents, of CCK and VIP were similarly reduced. Tissue weights throughout the gut were 1/2 or less than those of control rats. Since VIP but not CCK concentrations in the gut of MMI-treated animals were significantly greater than those of the control animals, it would appear that there was greater loss of mucosal tissue with its endocrine content of CCK than of neuronal tissue with its greater content of VIP.(ABSTRACT TRUNCATED AT 250 WORDS)
Capillary gas chromatography of cellular fatty acids and alcohols has been used as a routine method for a period of two years in the mycobacterial diagnostic laboratory of Statens institutt for folkehelse, Oslo, Norway. All mycobacteria (165 isolates) other than Mycobacterium tuberculosis (MOTT) and 24 randomly selected M. tuberculosis isolates were studied. Twelve characteristic lipid constituents allowed the construction of a diagnostic scheme. Without exceptions, all 36 examined isolates belonging to the M. tuberculosis-complex were characterized by a relatively high concentration level of hexacosanoic acid (mean: 4%, range: 1-13%), low level of tetracosanoic acid (mean: 1%, range: 0.1-3%), lack of methylbranched acids other than tuberculostearic acid, and lack of fatty alcohols. Members of the MAIS-complex (73 isolates) were all characterized by the general presence of the fatty alcohols 2-octadecanol (mean: 2%, range: 0.1-5%) and 2-eicosanol (mean: 7%, range: 2-21%), relatively high levels of tetracosanoic acid (mean: 5%, range: 1-15%) and lack (or trace) of hexacosanoic acid and methylbranched acids other than tuberculostearic acid. All 16 isolates of M. gordonae were easily recognized by their unique lack of tuberculostearic acid and their content of 2-methyl-tetradecanoic acid (mean: 5%, range: 2-12%), and the M. xenopi isolates were the only examined strains containing the fatty alcohol 2-docosanol (mean: 9%, range: 2-13%). The six M. malmoense strains contained the two unique constituents 2-methyl eicosanoic acid (mean: 3%, range: 1-4%) and 2,4,6-trimethyl tetracosanoic acid (mean: 3%, range: 2-4%). The ten strains of M. kansasii were characterized by 2,4-dimethyl tetradecanoic acid (mean: 5%, range: 1-11%), whereas the seven strains of M. marinum shared 2,4-dimethyl hexadecanoic acid (mean: 4%, range 0.2-12%) as a specific marker.
Nine cases of primary sternal tumour were retrospectively reviewed in regard to clinical, radiologic and surgical features. The tumours were chondrosarcoma (4), chondroma (3), solitary plasmacytoma (1) and osteochondroma (1). All the benign lesions were excised without complication or recurrence. Three chondrosarcomas were radically excised en bloc, and one was only locally excised because of gross involvement of underlying structures. The solitary plasmacytoma was treated with incisional biopsy and radiotherapy. Two of the three patients with radical excision of sternal chondrosarcoma were alive after 5 years. Careful preoperative assessment, including use of computed tomography, is important. Wide excision should be the procedure of choice for all sternal tumours, since differentiation between benign and malignant lesions may be difficult in cartilaginous tumours, which are the commonest types.
Primary malignant melanoma of the esophagus is an uncommon neoplasm. The world literature reports only 139 cases. It is mainly a disease of older age, predominantly in the 6th and 7th decades, with a male-to-female ratio of 2 to 1. Of all published cases, 60 (43.16%) occurred in the lower third, 40 (28.77%) in the middle third, 25 (17.98%) at the junction of the middle and lower thirds, and 14 (10.07%) in the upper third. Dysphagia was the commonest symptom and was found in 79.5% of cases. The tumors were polypoid, pedunculated, often pigmented, and usually presented as clinically advanced neoplasms. The histological and cytological features were similar to those of lentigo maligna melanoma, but with a more aggressive biological behavior. Hematogenous and lymphatic metastases were common. The overall survival was 9.8 months, and two-thirds of the patients died within a year of diagnosis, irrespective of therapeutic modalities. Deaths were disease-related in 85% of cases. It is concluded that, for operable patients, radical surgical resection is the treatment of choice, either for palliation or for cure, with a 5-yr survival of 4.2%. Irradiation is useful as a palliative or adjuvant measure. The roles of chemotherapy and immunostimulation need further evaluation.
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The cDNA for porcine preprocholecystokinin (pre-pro-CCK) was engineered for expression in mammalian cells under the control of the Rous sarcoma virus-long terminal repeat promoter. This expression construct was transfected into the murine anterior pituitary cell line, AtT-20. A stable cell line (AtT-20/CCK) was derived that expresses CCK mRNA indistinguishable from the CCK mRNA found in pig brain or gut. The AtT-20/CCK cells carry out proteolytic processing and sulfation reactions to generate authentic sulfated CCK8 from pro-CCK. The cells also store and secrete CCK-immunoreactive peptides. This secretion can be stimulated with corticotropin releasing factor, the natural secretagogue for anterior pituitary cells. In contrast, monkey kidney epithelial cells (COS cells), which are transiently transfected to express CCK, predominantly secrete nonsulfated pro-CCK into the medium. These studies show that a murine neuroendocrine cell line contains the complete processing machinery required to generate authentic porcine CCK8. The processing events include simultaneous proteolytic processing at one and two basic amino acid sites and sulfation of tyrosine residues. The cell line thus duplicates exactly the processing patterns found to occur in pig brain cortex.
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Previous studies have shown that pig intestine contains a 69 amino acid glucagon (glicentin) as well as a 37 amino acid glucagon (oxyntomodulin). In pig pancreas the 29 amino acid glucagon predominates. Since glucagon is thought to be expressed from a single gene in mammals, these differences in molecular forms indicate differential posttranslational processing of the glucagon precursor by different tissues. In the current study glucagon immunoreactivity (IR) was separately purified from dog pancreas, stomach mucosa and ileum mucosa. Purification and sequence analysis of the different tissue glucagons show that dog pancreas and stomach mucosa contain glucagon-29 while ileum mucosa contains glucagon-37 and glucagon-69. The latter is the major form present with glucagon-37 accounting for only 10-20% of the total ileum glucagon content. The N-terminal 32 amino acid portion of dog glucagon-69 differs at 6 sites from pig glucagon-69: RSLQDTEEKSRSFSAPQTEPLNDLDQMNEDKR... The C-terminal glucagon-37 is identical to pig oxyntomodulin.
We examined maximum expiratory flow (Vmax) in two canine preparations in which regional changes in lung mechanical properties were produced. In one experiment serial bronchial obstructions were made to determine whether flow-limiting sites (choke points, CP) would occur in series. With the right lung tied off, constrictions were placed at the left lower lobar bronchus (LLL) and left main-stem bronchus. On deflation from total lung capacity, the obstructed LLL and nonobstructed left upper lobe (LUL) emptied into the obstructed left main-stem bronchus. Although a CP common to both lobes was identified at the main-stem obstruction, which limited total Vmax, we questioned whether there was also a CP at the lobar obstruction that fixed LLL flow. In that case the rate of LLL emptying would not be dependent on the presence of the common (i.e., central) CP and thus the flow contribution of the LUL. We found that when the LUL was removed, the LLL increased its rate of emptying. Thus a lobar CP did not fix LLL flow and CP did not occur in series. In a second experiment emphysema was produced in the left lung to reduce lung recoil, whereas the right lung was normal. CP were identified at approximately lobar bronchi of each lung, and the lungs were emptied at different rates. A CP common to both lungs was not identified. Our results indicate that in localized lung disease, if flows from the different regions are high enough, then wave speed is reached in proximal airways, and a CP occurs centrally rather than peripherally. On the other hand, if flows are low, then wave speed is reached peripherally and a CP common to all lung regions does not occur.
We examined the effect of aminophylline on left ventricular (LV) mechanics and central hemodynamics under normoxic and hypoxic conditions in respective groups of dogs. In an open-chest preparation, LV end-systolic and diastolic dimensions were measured with ultrasonic crystal transducers seated subendocardially along the anterior to posterior and apex to base axes. In the group studied during hypoxia, measurements were obtained during 3 conditions: normoxia; hypoxia to a PO2 of 30 mm Hg; and during hypoxia when aminophylline was infused to a blood level of about 15 mg/L. In the group studied under normoxic conditions, measurements were initially obtained during normoxia after which aminophylline was also infused to a blood level of 15 mg/L. Intravascular volume was given or removed to maintain LV filling pressures at about 10 mm Hg during all conditions. In the normoxic group, aminophylline caused an increase in stroke volume (SV) and had a positive inotropic effect on the LV. End-systolic dimensions were reduced, while end-diastolic dimensions did not change with aminophylline. On the other hand, under hypoxic conditions, aminophylline did not have a positive inotropic effect: SV did not increase and end-systolic dimensions remained unchanged. Under hypoxic conditions, moreover, aminophylline caused a slight decrease in end-diastolic dimensions by augmenting hypoxia-induced increases in myocardial resting tension. Our results indicate that unlike normoxic conditions, aminophylline may have little beneficial effect on LV performance during hypoxic conditions.
Using previously cloned cDNAs to pig brain prepro-cholecystokinin mRNA and slot blot and S1 nuclease protection assays, the relative cholecystokinin mRNA levels in different regions of the pig brain were measured. The relative amounts of cholecystokinin mRNA generally correlated well with the levels of cholecystokinin-immunoreactive peptides in the various regions tested. One clear exception was noted in the cerebellum; in this region, levels of cholecystokinin mRNA were about 20% of the levels in brain cortex (or second highest level in all areas tested) whereas the mature forms of cholecystokinin peptides (cholecystokinin 58, cholecystokinin 8) were undetectable (less than 3 pmol/g). In vitro translation of cerebellar and cortical cholecystokinin mRNA indicated that there was no difference in the efficiency with which these two RNAs were translated into immunoreactive prepro-cholecystokinin. DNA sequence analysis confirmed that a cloned full-length cerebellar cholecystokinin cDNA was indistinguishable from its cortical counterpart and, therefore, must encode an identical prepro-cholecystokinin. We conclude that there are pronounced regional differences in cholecystokinin expression in pig brain. The apparent discrepancy between levels of immunoreactive cholecystokinin peptides and cholecystokinin mRNA in the cerebellum could be explained by a high turnover rate for the peptides, differential processing of the peptides, or tissue-specific inhibition of cholecystokinin mRNA translation.
Secretin was purified from the first 50 cm of proximal intestine of a single dog. The purification sequence included extraction in acid-ethanol, differential precipitation with acetone, Sephadex gel filtration and three successive HPLC steps. Dog secretin has the following sequence: HSDGTFTSELSRLRESARLQRLLQGLV. The underlined amino acid represents a substitution of Glu for Asp at position 15 from the NH2-terminus of pig secretin. Dog secretin is equal in potency to pig secretin in stimulating pancreatic ductal flow in a rat bioassay system.
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