Review of canine transmissible venereal sarcoma.
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Animals↗
Biomedical subjects
A K Das
Publications and source records attributed to A K Das.
A systematic analysis of factors which may impact upon tomographic perfusion imaging measurements: implications for the use of Tc-99m sestamibi in acute myocardial infarction.
BACKGROUND: The use of acute Tc-99m sestamibi imaging has provided a valuable methodology to assess myocardium at risk and collateral blood flow. OBJECTIVE: The purpose of this study was to determine the impact of physical, physiologic, and reconstruction factors on the extent and severity of Tc-99m sestamibi images in a porcine model of coronary occlusion and reperfusion. METHODS AND RESULTS: Eleven pigs underwent 40 min of coronary occlusion using a balloon catheter followed by reperfusion. Radiolabeled microspheres were injected during occlusion for blood flow determination and 20-30 mCi of Tc-99m sestamibi was injected intravenously for cardiac imaging. Each animal underwent four modes of gamma camera imaging: a cardiac and respiratory gated SPECT study, an ungated SPECT study, a post-mortem SPECT study and an ex-situ study where the heart was sliced into five short axis slices and directly imaged. All animals had extensive wall motion abnormalities at the time of imaging. Myocardial risk area by ex-situ imaging was 32 +/- 9% LV and did not significantly change with the addition of a chest cavity and tomographic reconstruction (post-mortem and gated imaging) or cardiac and respiratory motion (ungated imaging). Defect severity was significantly underestimated with the addition of a chest cavity and tomographic reconstruction but was unaltered by cardiac and respiratory motion. CONCLUSIONS: The assessment of risk area acutely by SPECT Tc-99m sestamibi imaging is unaffected by cardiac motion obviating the necessity for gated imaging. Estimated defect severity (which has been used as a measure of collateral flow) is significantly reduced by the chest wall and tomographic acquisition and reconstruction suggesting a role for scatter and attenuation algorithms for this measure.
Animals↗
Transvesical polytetrafluoroethylene graft: an unusual complication in urology.
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Aged↗
Sacral neuromodulation in the treatment of urgency-frequency symptoms: a multicenter study on efficacy and safety.
PURPOSE: Neuromodulation of sacral nerves has shown promising results in correcting voiding dysfunction. We report the results of a multicenter trial designed to assess the efficacy of sacral nerve neuromodulation in patients presenting with refractory urinary urgency-frequency. MATERIALS AND METHODS: A total of 51 patients from 12 centers underwent baseline assessment, including a detailed voiding diary, urodynamic evaluation and percutaneous test stimulation of the sacral nerves at S3 and/or S4. All patients enrolled in the study had undergone prior conventional treatment, such as pharmacotherapy, hydrodistention and surgical intervention, which failed. All patients demonstrated a satisfactory response to trial stimulation and were randomly divided into a stimulation group (25 patients) and a control group (26). A sacral nerve stimulation device was implanted after 6 months in the control group. Patients were followed at 1, 3 and 6 months, and at 6-month intervals for up to 2 years after implantation of a neuroprosthetic InterStim* system. dagger The study variables included the number of voids daily, volume voided per void and degree of urgency before void. RESULTS: Compared to the control group, 6-month voiding diary results demonstrated statistically significant improvements (p <0.0001) in the stimulation group with respect to the number voids daily (16.9 +/- 9.7 to 9.3 +/- 5.1), volume per void (118 +/- 74 to 226 +/- 124 ml.) and degree of urgency (rank 2.2 +/- 0.6 to 1.6 +/- 0.9). Patients in the control group showed no significant changes in voiding parameters at 6 months. Significant improvements in favor of the stimulation group were noted in various parameters with respect to water cystometry and quality of life (SF-36). At 6 months after implant, neurostimulators were turned off in the stimulation group and urinary symptoms returned to baseline values. After reactivation of stimulation sustained efficacy was documented at 12 and 24 months. CONCLUSIONS: Neuromodulation of the sacral nerves is an effective, safe therapy that successfully treats significant symptoms of refractory urgency-frequency.
Adult↗
Rabbit urinary bladder blood flow changes during the initial stage of partial outlet obstruction.
PURPOSE: The rabbit urinary bladder's early response to partial outlet obstruction includes bladder wall remodeling with marked urothelial and fibroblast hyperplasia (1 day) and smooth muscle hypertrophy (3-5 days) resulting in a 4-5 fold increase in bladder mass within 7 days. In this study, we examined the effect of partial outlet obstruction on bladder blood flow during the initial period of rapid growth (1-7 days). MATERIALS AND METHODS: Each New Zealand White rabbit was partially obstructed by tying a 2-0 silk ligature loosely around the vesical outlet. After 0 (unoperated), 4 hours, 1, 3, or 7 days of obstruction, 5 rabbits per group were anesthetized and the carotid and femoral arteries cannulated with polyethylene tubing. Additional rabbits receiving sham surgeries were treated like obstructed animals at 4 hours and 1 day post-obstruction (5/group). Using standard methods, fluorescent microspheres were infused through the right carotid artery. Bladder and right kidney were rapidly removed upon completion of sphere infusion; bladder mucosa and muscle were separated. Sphere densities in detrusor, mucosa, and kidney were measured by Interactive Medical Technologies, Ltd. A section of each detrusor tissue was fixed in formalin and immunostained for smooth muscle alpha-actin. RESULTS: Mucosal blood flow (0.20 +/- 0.03 ml./min./gm.) was approximately 4-fold greater than that of detrusor (0.05 +/- 0.01 ml./min./gm.). Sham surgery caused a significant increase in bladder blood flow at 4 hours post-obstruction that returned to control levels by 1 day. Both mucosal and muscle blood flows were slightly higher in rabbit bladders obstructed for 4 hours than in sham-operated rabbits, and substantially greater in those obstructed for 1 day: 0.68 +/- 0.13 ml./min./gm. (mucosa) and 0.26 +/- 0.04 ml./min./gm. (muscle). Blood flows returned to control values by 3 days post-obstruction and remained constant through 7 days. Kidney blood flow was unchanged. Although bladder weight increased 4-fold after 7 days of obstruction, the volume fraction of smooth muscle (transverse section) remained constant at approximately 40%. CONCLUSIONS: Blood flow was approximately 4-fold greater in bladder mucosa than in muscle, which may relate to the significantly higher metabolic rate and lower high energy phosphate concentration of mucosa than muscle. Partial outlet obstruction resulted in a significant increase in blood flow at 1 day post-obstruction, which coincides temporally with the early cellular hyperplasia and hypertrophy of obstructed rabbit bladder. This increase in blood flow may be an essential factor for the initial increase in bladder mass. By three days, the blood flow per gram of tissue returned to control levels. The mechanisms relating to the changes in blood flow induced by partial outlet obstruction are currently under investigation.
Animals↗
Randomized controlled trial on the effective dose of anti-snake venom in case of snake bite with systemic envenomation.
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Acute Kidney Injury↗
Sacral nerve stimulation for the management of voiding dysfunction.
Voiding dysfunction is common, and patients with urge incontinence, frequency/urgency syndromes, and chronic urinary retention are challenging to treat once conservative therapies (such as pharmacologic agents, pelvic floor rehabilitation, and intermittent catheterization) have been exhausted. Sacral nerve stimulation (SNS) is a new, minimally invasive, reversible therapy for the management of refractory voiding dysfunction and provides an attractive therapeutic alternative for patients with this condition. In this review, the role of SNS in the management of voiding dysfunction is examined critically, and the efficacy, risks, and benefits of this new modality are evaluated.
Journal Article↗
Studies on antidiarrhoeal activity of Punica granatum seed extract in rats.
Methanol extract of Punica granatum seed was evaluated for antidiarrhoeal activity against different experimental models of diarrhoea in rats. P. granatum seed extract treated animals showed significant inhibitory activity against castrol-oil induced diarrhoea and PGE2 induced enteropooling in rats. The extract also showed a significant reduction in gastro-intestinal motility in charcoal meal test in rats. The results obtained established the efficacy of P. granatum seed extract as an antidiarrhoeal agent.
Animals↗
Flow cytometric determination of cell proliferation in hypertensive blood vessels.
BACKGROUND: Measurement of vascular cell proliferation in animal models of hypertension is currently accomplished by demonstrating [(3)H]-thymidine ([(3)H]-dT) incorporation into DNA using autoradiography. This method, however, is labor intensive, requires radioactivity, and is limited by the inherent difficulty in discriminating labeled and unlabeled cells. To address these limitations, a flow cytometric-based method is described utilizing incorporation of 5-bromo-2'-deoxyuridine (BrdU) into DNA of nuclei isolated from blood vessels. METHODS: Pulmonary hypertension was induced in rats by exposure to 10% O(2) (hypoxia) for varying periods of time. Pulmonary arteries and aorta from rats injected with BrdU prior to sacrifice were isolated, fixed with 10% formalin, and digested with Protease XIV. The intact nuclei liberated by this treatment were successively treated with HCl/Triton X-100 and sodium borate. Processed nuclei were probed with a BrdU-specific fluorescein-conjugated antibody, and the percentage of BrdU staining cells was determined using flow cytometry. RESULTS: An approximately 20-fold increase in BrdU-positive cells at 3 days of hypoxia in pulmonary arteries (relative to control) with no change in aorta was observed. These results were similar to previous studies using [(3)H]-dT labeling. CONCLUSIONS: Flow cytometric determination of cell proliferation in blood vessels is a simple, objective technique that may facilitate measurement of cell proliferation in animal models of vascular disease.
Animals↗
Mapping of a palmitoylatable band 3-binding domain of human erythrocyte membrane protein 4.2.
Evidence accumulated over the years suggests that human erythrocyte membrane protein 4.2 is one of the proteins involved in strengthening the cytoskeleton-membrane interactions in the red blood cell. Deficiency of protein 4.2 is linked with a variety of hereditary haemolytic anaemia. However, the interactions of protein 4.2 with other proteins of the erythrocyte membrane remain poorly understood. The major membrane-binding site for protein 4.2 resides on the cytoplasmic domain of band 3 (CDB3). In order to carry out an initial characterization of its interaction with the CDB3, protein 4. 2 was subjected to proteolytic cleavage and gel renaturation assay, and the 23-kDa N-terminal domain was found to interact with band 3. This domain contained two putative palmitoylatable cysteine residues, of which cysteine 203 was identified as the palmitoylatable cysteine. Recombinant glutathione S-transferase-fusion peptides derived from this domain were characterized with respect to their ability to interact with the CDB3. Whereas these studies do not rule out the involvement of other subsites on protein 4.2 in interaction with the CDB3, the evidence suggests that the region encompassing amino acid residues 187-211 is one of the domains critical for the protein 4.2-CDB3 interaction. This is also the first demonstration that palmitoylation serves as a positive modulator of this interaction.
Amino Acid Sequence↗
Genotype-phenotype correlations in neuronal ceroid lipofuscinosis due to palmitoyl-protein thioesterase deficiency.
The infantile form of neuronal ceroid lipofuscinosis (NCL) has been well studied in Finland, where there is a high carrier frequency (1:70) for a single mutation in the causative gene, CLN1, or PPT. We have recently studied a group of 29 NCL subjects in the United States with palmitoyl-protein thioesterase (PPT) deficiency and described 19 different CLN1/PPT mutations in our population. In this report, we present a review of our previous findings, including a more detailed analysis of phenotype-genotype correlations, and present previously unpublished data concerning the clinical manifestations of the disorder in children of families with multiple affected members. Our studies indicate that about half of PPT-deficient patients in the United States are very similar to Finnish infants with INCL, but that a different mutation (R151X) accounts for 40% of U.S. alleles. The Finnish mutation (R122W) is rare in the United States. The other half of U.S. PPT-deficient patients develop symptoms after the age of 2 years, much later than Finnish patients. One common mutation (the "Scottish" allele, T75P) accounts for 13% of alleles and results in a juvenile-onset phenotype that is clinically indistinguishable from JNCL with CLN3 mutations. Other rare mutations were also associated with JNCL phenotypes, such as D79G and G250V. A preliminary expression study of two of these mutant enzymes supports the conclusion that juvenile-onset NCL (JNCL with GROD) is caused by missense mutations in the PPT gene that result in mutated enzymes with residual PPT enzyme activity.
Age of Onset↗
Biochemical evaluation of obstructive bladder dysfunction in men secondary to BPH: a preliminary report.
OBJECTIVES: In the rabbit, two of the major cellular alterations that mediate bladder dysfunction secondary to partial outlet obstruction are a decreased ability of the sarcoplasmic reticulum (SR) to store and release Ca2+, and mitochondrial dysfunction. The objective of the current study was to determine whether SR and mitochondrial dysfunctions are associated with symptomatic benign prostatic hyperplasia (BPH) in men. METHODS: Bladder biopsies were obtained from men with symptomatic BPH and from age-matched men with no urologic dysfunction. Each biopsy was analyzed for the following enzyme activities: malate dehydrogenase and citrate synthase (mitochondrial markers) and the sarcoplasmic reticular enzyme Ca2+ -dependent adenosine triphosphatase (ATPase). These values were compared with the enzyme activities of control rabbit bladder smooth muscle and bladder smooth muscle obtained from rabbits subjected to 2 weeks of partial outlet obstruction. RESULTS: The enzymatic activities of all three enzymes are significantly lower in human bladder smooth muscle than in rabbit bladder smooth muscle. The maximal activities of all three enzymes are significantly lower in human bladder samples obtained from men with diagnosed obstructive uropathy than in men of equal age with no urologic dysfunction. CONCLUSIONS: These studies demonstrate that similar to the response of the rabbit to partial outlet obstruction, obstructive dysfunction secondary to BPH is characterized by mitochondrial and SR dysfunction.
Animals↗
Variable extrathoracic airflow obstruction and chronic laryngotracheitis in Gulf War veterans.
STUDY OBJECTIVES: To study the flow-volume loop for evidence of variable extrathoracic airflow obstruction in Persian Gulf War veterans. DESIGN: Retrospective case-control, single-center study. SETTING: The pulmonary division of an academic health-care center. SUBJECTS: A convenience sample of the Persian Gulf Registry. MEASUREMENTS AND INTERVENTIONS: (1) Midvital capacity ratio (ratio of maximum forced midexpiratory to maximum forced midinspiratory flow). This ratio is the criterion standard for the diagnosis of variable extrathoracic airflow obstruction. (2) Evaluation of the anatomy and function of the extrathoracic airway by fiberoptic bronchoscopy. (3) Further investigation into the airway abnormality by histologic evaluation of tracheal biopsy samples in Gulf War veterans only. RESULTS: Midvital capacity was > 1.0 in 32 of 37 Gulf War veterans compared with only 11 of 38 control subjects. The mean (+/-SD) value was 1.37+/-0.4 among Gulf War veterans and 0.88+/-0.3 among control subjects (p=0.0000005). FVC and its ratio to FEV1 were normal in all these subjects. Bronchoscopy showed inflamed larynx and trachea in all (n=17) Gulf War veterans. Histologic study showed chronic inflammation of the trachea in everyone (n=12) who had an adequate biopsy sample. CONCLUSION: Physicians should be made aware of the presence of chronic inflammation of the upper airways and inspiratory airflow limitation in a number of Gulf War veterans.
Adolescent↗
Clinical and laboratory profile of diabetes in elderly.
India is amidst a demographic transition showing an ageing trend. This will increase non-communicable diseases including diabetes which is already showing an increasing trend. With scanty literature existing on elderly diabetics (> 60 years of age), it was decided to study the clinico-laboratory and complication profile of this group of patients. Fifty consecutive elderly diabetics were studied and evaluated for ECG, chest x-ray, blood sugar, urea, creatinine, lipid profile, proteinuria, motor nerve conduction velocity and autonomic neuropathy. Duration of diabetes varied from one month to 28 years. Fifty-six per cent of the patients presented with classical symptoms of polyuria, polyphagia and polydipsia. Hypertension was present in 40% and cataract in 54% of the patients. Eighteen per cent were obese, 52% had evidence of peripheral neuropathy while 56% had autonomic neuropathy. Background diabetic retinopathy was present in 56%, pre-proliferative retinopathy and maculopathy in 4% each; hypertensive retinopathy in 10% of patients; 44% had microproteinuria and 8% had chronic renal failure. Hypercholesterolaemia was present in 64% and hypertriglyceridaemia in 42% of the patients with 26% having coronary artery disease. Sixty per cent were harbouring infections--20% had foot infections, 14% had tuberculosis and 10% had urinary tract infections. Ninety-two per cent of the patients were aware of their disease but 62% were not aware of the complications and of the need for strict dietary and drug compliance. There was a high prevalence of associated diseases viz, osteoarthritis, cataract, hypertension, hepatitis and parkinsonism. Therefore, this study brings out the need to have a holistic and multidisciplinary approach for management of elderly diabetics who constitute a heterogeneous group with distinct health care problems.
Age Distribution↗
Molecular genetics of palmitoyl-protein thioesterase deficiency in the U.S.
Mutations in a newly described lysosomal enzyme, palmitoyl-protein thioesterase (PPT), were recently shown to be responsible for an autosomal recessive neurological disorder prevalent in Finland, infantile neuronal ceroid lipofuscinosis. The disease results in blindness, motor and cognitive deterioration, and seizures. Characteristic inclusion bodies (granular osmiophilic deposits [GROD]) are found in the brain and other tissues. The vast majority of Finnish cases are homozygous for a missense mutation (R122W) that severely affects PPT enzyme activity, and the clinical course in Finnish children is uniformly rapidly progressive and fatal. To define the clinical, biochemical, and molecular genetic characteristics of subjects with PPT deficiency in a broader population, we collected blood samples from U.S. and Canadian subjects representing 32 unrelated families with neuronal ceroid lipofuscinosis who had GROD documented morphologically. We measured PPT activity and screened the coding region of the PPT gene for mutations. In 29 of the families, PPT deficiency was found to be responsible for the neurodegenerative disorder, and mutations were identified in 57 out of 58 PPT alleles. One nonsense mutation (R151X) accounted for 40% of the alleles and was associated with severe disease in the homozygous state. A second mutation (T75P) accounted for 13% of the alleles and was associated with a late onset and protracted clinical course. A total of 19 different mutations were found, resulting in a broader spectrum of clinical presentations than previously seen in the Finnish population. Symptoms first appeared at ages ranging from 3 mo to 9 yr, and about half of the subjects have survived into the second or even third decades of life.
Adolescent↗
The structure of the tetratricopeptide repeats of protein phosphatase 5: implications for TPR-mediated protein-protein interactions.
The tetratricopeptide repeat (TPR) is a degenerate 34 amino acid sequence identified in a wide variety of proteins, present in tandem arrays of 3-16 motifs, which form scaffolds to mediate protein-protein interactions and often the assembly of multiprotein complexes. TPR-containing proteins include the anaphase promoting complex (APC) subunits cdc16, cdc23 and cdc27, the NADPH oxidase subunit p67 phox, hsp90-binding immunophilins, transcription factors, the PKR protein kinase inhibitor, and peroxisomal and mitochondrial import proteins. Here, we report the crystal structure of the TPR domain of a protein phosphatase, PP5. Each of the three TPR motifs of this domain consist of a pair of antiparallel alpha-helices of equivalent length. Adjacent TPR motifs are packed together in a parallel arrangement such that a tandem TPR motif structure is composed of a regular series of antiparallel alpha-helices. The uniform angular and spatial arrangement of neighbouring alpha-helices defines a helical structure and creates an amphipathic groove. Multiple-TPR motif proteins would fold into a right-handed super-helical structure with a continuous helical groove suitable for the recognition of target proteins, hence defining a novel mechanism for protein recognition. The spatial arrangement of alpha-helices in the PP5-TPR domain is similar to those within 14-3-3 proteins.
14-3-3 Proteins↗
Use of abdominal fascia to create partial outlet obstruction in rabbits.
Partial outlet obstruction has been used for a considerable period of time as an animal model for the urodynamic changes that occur with the progressive obstruction of benign prostatic hyperplasia (BPH). Although there are many models of partial outlet obstruction, one common feature is that the degree of obstruction produced is inconsistent. The current study evaluates the responses of the bladder to a partial outlet obstruction created using an autologous fascial collar from harvested rectus fascia. The results demonstrate that although there was a moderate and variable increase in bladder mass, the alterations in the contractile responses to field stimulation (FS), carbamyl choline (carbachol), KCl, and adenosine 5'-triphosphate (ATP) were less severe than other models of partial outlet obstruction. Specifically, there was an approximate 40% decrease in the magnitude of the contractile response to FS but no significant changes in the magnitude of the contractile responses to carbachol, KCl, or ATP. Further analysis of the contractile responses demonstrated that there was a greater decrease in the rate of tension generation than in the magnitude of response for FS, and a significant increase in the time to maximal tension. Although there were no decreases in the magnitude of the responses to carbachol, KCl, or ATP, there were significant reductions in the rate of tension generation for carbachol and KCl and significant increases in the time to maximal tension for carbachol and ATP. Applying less tension over a wider area, the fascial collar provided a consistent and reproducible mild partial outlet obstruction.
Adenosine Triphosphate↗
Treatment of biliary calculi using holmium: yttrium aluminum garnet laser.
BACKGROUND: The holmium: yttrium aluminum garnet laser (Ho: YAG) has been shown to be effective and safe for the treatment of urinary calculi. Its effectiveness for the treatment of biliary calculi was investigated. METHODS: Endoscopic Ho: YAG lithotripsy of biliary stones was performed 7 times in 4 patients. Two patients had biliary duct calculi, and the other two patients had gall bladder calculi. All patients had multiple calculi that ranged in size from 4 mm to 5 cm. All procedures were performed percutaneously under intravenous sedation and local anesthesia. Rigid and flexible endoscopes were used to access the biliary calculi. Postoperative cholangiograms were performed on all patients. RESULTS: All calculi were successfully fragmented with the Ho: YAG laser. The most common settings on the laser were 1.0 J and 10 Hz. Average total laser energy used was 12.24 kJ. Two patients required multiple procedures for the resolution of the biliary calculi. No vascular or biliary injuries were encountered. Three patients were free of biliary calculi on their postoperative cholangiogram. One patient with multiple gallbladder stones refused further treatment after two percutaneous procedures. CONCLUSION: The holmium: yttrium aluminum garnet laser can be used safely and effectively in the endoscopic treatment of biliary calculi. This treatment maybe a suitable option in patients who are not candidates for more invasive procedures.
Adult↗