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Biomedical subjects

S K Gupta

Publications and source records attributed to S K Gupta.

At least 505 records · Page 28Linked to original sources

Unsuspected preexisting saphenous vein disease: an unrecognized cause of vein bypass failure.

Our prior anecdotal experience with unsuspected preexisting saphenous vein disease prompted us to study its incidence, its relation to graft failure, and to identify techniques for its detection. Thick-walled, postphlebitic sclerotic occluded, postphlebitic sclerotic recanalized, calcified, and varicose vein lesions were detected in 63 (12%) of 513 infrainguinal vein bypasses. In 13 (2% to 5%) cases, severe saphenous vein disease precluded use of the vein. In the remaining 50 cases, the entire vein or a portion thereof, with minimal or unsuspected disease, was used for bypass. Early graft failures occurred in 10 (20%) of the 50 cases. The cumulative primary patency rate at 30 months for bypasses performed with diseased veins was 32%. This was significantly less than the 73% cumulative primary patency rate for bypasses with veins without detectable disease (p less than or equal to 0.001). Retrospective evaluation of preoperative duplex ultrasonography (n = 21) originally used to evaluate saphenous vein length and diameter correctly identified thick-walled, occluded, calcified, and varicose veins in 62% of cases. Intraoperative methods of vein evaluation included inspection, palpation, irrigation, catheter or valvulotome insertion to identify obstruction, and intraoperative arteriography. Histologic examination of diseased veins demonstrated a spectrum of disease with thickening of the intima and media, vein wall calcification, and luminal recanalization. We conclude that (1) unsuspected preexisting saphenous vein disease occurs in approximately 12% of cases and results in both early and late graft failures; (2) detection, in some cases, is possible with duplex ultrasonography and intraoperative techniques; and (3) diseased veins that are recanalized, calcified, or thick-walled should not be used if an alternative vein is available.

Chi-Square Distribution↗

A twelve-year experience with the popliteal-to-distal artery bypass: the significance and management of proximal disease.

The value of the popliteal-to-distal artery bypass in limb salvage is well documented. However, the influence of progression of disease in the superficial femoral artery or proximal popliteal artery, and the role of percutaneous transluminal angioplasty of these vessels before bypass have not been adequately assessed. To evaluate these and other factors, we reviewed our experience with 153 nonsequential popliteal-to-distal artery bypasses performed over a 12-year period. Limb salvage was the indication for all procedures, and 87% of the patients were diabetic. The 5-year primary and secondary graft patency rates were 55% and 60%, respectively, and the limb salvage rate was 73%. Preoperative arteriograms were evaluated for stenosis in the superficial femoral artery or popliteal artery proximal to the graft. Fifty-six grafts with a proximal stenosis 20% or less were identified and had primary graft patency of 77% at 2 years, similar to the 70% patency for the 20 grafts placed distal to a 21% to 35% stenosis. The 18 grafts placed distal to a stenosis greater than 35% had 53% 2-year primary graft patency (p = 0.25). Percutaneous transluminal angioplasty of a superficial femoral artery or popliteal artery stenosis (24% to 85% luminal narrowing) in 19 limbs resulted in 68% 2-year graft patency, not significantly lower than grafts with 35% or less proximal stenosis (75%, p = 0.25). Other factors associated with significant decreases in graft patency included a vein graft diameter less than 3.0 mm, a dorsalis pedis outflow site, and poor quality outflow. Thus the popliteal-to-distal bypass is a durable procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Developmentally regulated alternative RNA splicing of rat brain sodium channel mRNAs.

Two rat brain Na channel alpha-subunit cDNAs, named RII and RIIA, have almost identical coding regions, with a divergence of only 36 nucleotides (0.6%) over a total length of 6015 residues. A cluster of 20 divergent residues occurs within a 90 nucleotide segment of cDNA sequence. We now demonstrate that this 90 nucleotide segment is encoded twice in the RII/RIIA genomic sequence. Furthermore, the mutually exclusive selection of these two exons is developmentally regulated. RII mRNAs are relatively abundant at birth but are gradually replaced by RIIA mRNAs as development proceeds. The two mRNAs also appear to have different regional distributions in the developing rat brain. Strikingly, although 30 amino acids are encoded by each alternative exon, only amino acid position 209 is altered between the two, specifying asparagine in RII and aspartate in RIIA. Alternative RNA splicing may modulate the RII/RIIA sodium channel properties during neuronal development.

Amino Acid Sequence↗

GTPase-deficient G alpha i2 oncogene gip2 inhibits adenylylcyclase and attenuates receptor-stimulated phospholipase A2 activity.

The GTPase activity of a G protein alpha subunit functions as a timer to control the lifetime of the activated conformation of the protein. Expression of the GTPase-deficient Gi2 alpha subunit oncogene, gip2 (alpha i2Q205L), in Chinese hamster ovary cells inhibited the stimulation of adenylylcyclase and altered the calcium regulation of the Gi2-phospholipase A2 (PLA2) effector complex. The phenotypic consequence of the activated alpha i2 mutant on hormonal stimulation of PLA2 varied depending on the cytoplasmic calcium transient elicited by different Gi2-linked receptors. The stimulation of PLA2 by thrombin, which mobilized calcium only from internal stores, was markedly attenuated in gip2-expressing cells. In contrast, the attenuation of the PLA2 response to ATP, a purinergic agonist which mobilizes calcium from both extracellular space and internal stores, was significantly less than that observed for thrombin. Ionomycin, a calcium ionophore, stimulated PLA2 activity in clones which expressed gip2 to a level similar to that observed in wild-type Chinese hamster ovary cells. Thus, the dominant GTPase-deficient gip2 polypeptide will constitutively inhibit adenylylcyclase but differentially modulate enzymes regulated by calcium and coupled to Gi2.

Adenosine Triphosphate↗

Mutation and selection during the secondary response to 2-phenyloxazolone.

The most characteristic feature of the mouse antibody response to the hapten 2-phenyloxazolone is the recurrent expression of the light-chain variable region Igk-VO chi 1 gene in its germ-line or mutated configuration. The analysis of somatic mutants of the Igk-VO chi 1 gene reported here indicates that, as found during the primary response, hypermutation is also activated during the secondary response. Somatic mutations in the Igk-VO chi 1 gene increased in sequences obtained at day 14 and day 21 in the primary response and again in the secondary response at days 3, 5, and 7. The ratio of replacement to silent mutations also increased, particularly between days 5 and 7, suggesting that a stage of negative selection operates on new somatic mutants generated in the secondary response. Most Igk-VO chi 1 mutants isolated in the secondary response had the features of selected memory clones (i.e., they carried mutations known to increase binding affinity for the hapten). However, some clones had chain-termination codons, and others had mutations predicting a nonfunctional light chain. At least three and possibly five of these clones also expressed the mutation characteristic of the memory response to 2-phenyloxazolone (His-34----Asn-34/Gln-34). We conclude that after a second antigenic challenge, new somatic variants, including some leading to the loss of antigen binding, are generated by hypermutation of cells derived from the memory pool.

Amino Acid Sequence↗

FNA cytodiagnosis of non-Hodgkin's lymphoma and its subtyping under working formulation of 175 cases.

One hundred thirty-two cases diagnosed as non-Hodgkin's lymphoma (NHL) by fine-needle aspiration cytology (FNAC) and histology, and 43 cases in which there were minor or major discrepancies between cytology and histology for diagnosis of NHL, were reviewed. The diagnostic accuracy of FNAC for NHL was 86.3% at the initial diagnosis. Following review, all the 132 cases initially diagnosed as NHL by cytology and histology remained so with minor changes in subtypes in a few cases. Of the 43 discrepant cases, 28 turned out to be NHL and 6 as Hodgkin's disease (HD); 3 were anaplastic carcinoma; and in 6 cases the discrepancy still persisted. Diagnostic accuracy of FNA for NHL improved to 98.0% following review. Categorization of histologically diagnosed NHL cases under working formulation showed that 10.4%, 21.5%, and 57.7%, respectively, were low, intermediate, and high-grade lymphomas. The corresponding figures were 16.6%, 18.4%, and 60.1%, respectively, in cytology. The diagnostic accuracy of cytology for subtyping was found to be 67.5%.

Adolescent↗

Working formulation of the non-Hodgkin's lymphomas: a study of cell size and mitotic indices in cytologic subtypes.

Cell size and mitotic indices were studied in 243 non-Hodgkin's lymphomas (NHL) diagnosed cytologically and classified according to the Working Formulation. Low-, intermediate-, and high-grade lymphomas constituted 14.8%, 18.9%, and 61.7% of the cases, respectively. Measurement of the diameter of 100 lymphoid cells in each case showed that in most of the low-grade malignant lymphomas, 50-80% of the cells were small (less than 10 microns). A majority of the cells (an average of 45-60%) in intermediate- and high-grade lymphomas were in the range of 11-15 microns. Only the intermediate-grade large noncleaved and high-grade immunoblastic lymphomas had a majority of their cells (greater than 50%) larger than 15 microns. The mitotic indices (number of mitotic figures per 500 lymphoid cells) showed a highly significant difference between low- (0.7 +/- 1.14), intermediate- (3.0 +/- 2.67), and high-grade (5.4 +/- 3.40) lymphomas using the Wilcoxon's signed rank test (P less than 0.0001). Nearly two-thirds of the cases in each grade were within specific ranges of mitotic indices, i.e., less than 1 for low-, 1-3 for intermediate-, and greater than 3 for high-grade lymphomas.

Adolescent↗

Genetic and structural analysis of G protein alpha subunit regulatory domains.

Genetic and structural analysis of the alpha chain polypeptides of heterotrimeric G proteins defines functional domains for GTP/GDP binding, GTPase activity, effector activation, receptor contact and beta gamma subunit complex regulation. The conservation in sequence comprising the GDP/GTP binding and GTPase domains among G protein alpha subunits readily allows common mutations to be made for the design of mutant polypeptides that function as constitutive active or dominant negative alpha chains when expressed in different cell types. Organization of the effector activation, receptor and beta gamma contact domains is similar in the primary sequence of the different alpha subunit polypeptides relative to the GTP/GDP binding domain sequences. Mutation within common motifs of the different G protein alpha chain polypeptides have similar functional consequences. Thus, what has been learned with the Gs and Gi proteins and the regulation of adenylyl cyclase can be directly applied to the analysis of newly identified G proteins and their coupling to receptors and regulation of putative effector enzymes.

Adenosine Diphosphate Ribose↗

Activating mutations in the NH2- and COOH-terminal moieties of the Gs alpha subunit have dominant phenotypes and distinguishable kinetics of adenylyl cyclase stimulation.

The alpha subunit polypeptides of the G proteins Gs and Gi2 stimulate and inhibit adenylyl cyclase, respectively. The alpha s and alpha i2 subunits are 65% homologous in amino acid sequence but have highly conserved GDP/GTP binding domains. Previously, we mapped the functional adenylyl cyclase activation domain to a 122 amino acid region in the COOH-terminal moiety of the alpha s polypeptide (Osawa et al: Cell 63:697-706, 1990). The NH2-terminal half of the alpha s polypeptide encodes domains regulating beta gamma interactions and GDP dissociation. A series of chimeric cDNAs having different lengths of the NH2- or COOH-terminal coding sequence of alpha s substituted with the corresponding alpha i2 sequence were used to introduce multi-residue non-conserved mutations in different domains of the alpha s polypeptide. Mutation of either the amino- or carboxy-terminus results in an alpha s polypeptide which constitutively activates cAMP synthesis when expressed in Chinese hamster ovary cells. The activated alpha s polypeptides having mutations in either the NH2- or COOH-terminus demonstrate an enhanced rate of GTP gamma S activation of adenylyl cyclase. In membrane preparations from cells expressing the various alpha s mutants, COOH-terminal mutants, but not NH2-terminal alpha s mutants markedly enhance the maximal stimulation of adenylyl cyclase by GTP gamma S and fluoride ion. Neither mutation at the NH2- nor COOH-terminus had an effect on the GTPase activity of the alpha s polypeptides. Thus, mutation at NH2- and COOH-termini influence the rate of alpha s activation, but only the COOH-terminus appears to be involved in the regulation of the alpha s polypeptide activation domain that interacts with adenylyl cyclase.

Adenylyl Cyclases↗

Serum trace elements and Cu/Zn ratio in breast cancer patients.

Serum copper, zinc, and the Cu/Zn ratio were measured in 55 patients with breast disease (20 with benign breast diseases and 35 patients with breast cancer) and 30 controls. The mean serum copper levels were higher in breast cancer than in benign breast diseases (167.3 micrograms/dl vs. 117.6 micrograms/dl) (P less than 0.001) and controls (167.3 micrograms/dl vs. 98.8 micrograms/dl) (P less than 0.001). Patients with advanced breast cancer had higher serum copper levels than did patients with early breast cancer (177.9 micrograms/dl vs. 130.4 micrograms/dl) (P less than 0.001). The mean serum zinc levels were lowered only in patients with advanced breast cancer as compared with controls (88.6 micrograms/dl vs. 115.1 micrograms/dl) (P less than 0.001). Serum zinc levels were not decreased in patients with early breast cancer and benign breast diseases. The Cu/Zn ratio was increased in breast cancer patients (1.91 vs. 0.86) (P less than 0.001) but not in patients with benign breast diseases. The precise mechanisms responsible for the alterations in trace element levels in breast cancer patients are still unclear and require further evaluation. However, the serum copper levels and the Cu/Zn ratio may be used as biochemical markers in these patients.

Adult↗

Early experience with the smart laser in the treatment of atherosclerotic occlusions.

A dual-laser system (helium-cadmium and pulsed dye) capable of continuous computer analysis of spectroscopic characteristics of tissue fluorescence, which can distinguish atherosclerotic plaque from components of normal arterial wall, was used to deliver laser energy to ablate plaque. During a 1-year period this system was used to facilitate balloon angioplasty of short (3 to 17 cm) total occlusions of the superficial femoral or popliteal arteries only when standard angioplasty techniques were ineffective. During the year of the study, in one institution 415 patients were subjected to arteriography of the lower extremities for leg ischemia (397 for limb salvage indications). Standard angioplasty techniques were used in 94 of these patients; 218 patients were unsuitable for standard angioplasty, did not fulfill criteria for "smart" laser treatment, and underwent standard bypass operations. Only 11 patients (plus six others in the second institution) requiring treatment fulfilled the criteria for use of the "smart" laser. In 10 patients the occluding lesion was traversed by the laser wire (diameter 0.021 inch), and luminal patency was effectively restored by balloon angioplasty to greater than or equal to 70% of the most normal-appearing segment of that artery. Satisfactory luminal patency has persisted for 2 to 12 months (mean 6 months) in nine patients; the lesion in the tenth patient restenosed at 3 months. The laser procedure was unsuccessful in all three patients with occlusions greater than 10 cm and in four others. Although there were three microperforations with the laser wire, there were no clinically significant complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Unilateral aortofemoral bypass: a safe and effective option for the treatment of unilateral limb-threatening ischemia.

To determine whether unilateral aortofemoral (AUF) bypass is a safe and effective option for the treatment of unilateral limb-threatening ischemia in patients with aortic or bilateral iliac occlusive disease, we reviewed the results of 42 AUF bypasses performed using polytetrafluoroethylene grafts in patients operated on for limb salvage; 11 (26%) of the patients also underwent femoropopliteal or femorodistal (FP/D) bypasses. The indications for surgery were tissue necrosis or ulceration in 18 (43%) patients and rest pain in 17 (40%) patients. The 5-year primary graft patency and limb salvage rates for AUF bypass were 74% and 84%, respectively. The perioperative mortality rate was 5%. There were no significant differences in the primary graft patency or limb salvage rates in patients who underwent AUF bypass with or without FP/D bypass. Only 3 of 41 (7%) AUF bypass patients required subsequent femorofemoral bypass. We conclude that: (1) AUF bypass is a safe and effective surgical option in patients with unilateral limb-threatening ischemia and aortic or bilateral iliac occlusive disease; (2) the routine performance of an aortobifemoral or axillobifemoral bypass in patients with unilateral limb-threatening ischemia may be unnecessary; and (3) AUF bypass facilitates the combined inflow and infrainguinal operations that are frequently required for limb salvage in these patients.

Adult↗

Ultrastructural observations in testicular tissue of chromium-treated rats.

The administration of hexavalent chromium (2 mg/kg, ip as potassium dichromate) in adult rats daily for 15 days produced significant increases in the blood and testicular chromium levels. Although no light microscopic pathologic changes or alterations in epididymal sperm counts and motility were observed, lanthanum perfusion in treated rats revealed leakage of Sertoli-cell tight junctions under EM. A few tubules showed marked ultracellular alterations in the form of vacuolization of cytoplasm and degeneration of mitochondria in the epithelial cells. Late stage spermatids were the most affected germ cells. The mitochondrial sheath of the midpiece was vacuolated, incomplete, swollen, or broken in places. The observed alterations may result in the disruption of normal testicular physiology leading to reproductive impairment after chromium exposure.

Animals↗

Lead induced ultrastructural changes in the testis of rats.

Oral lead administration (250 ppm lead acetate through drinking water) to weaning male rats for 70 days resulted in the marked accumulation of this metal in blood and testicular tissue. No marked changes were evident in light microscopy. Ultrastructural changes were revealed in the form of vacuolisation of Sertoli cell cytoplasm and increase in the number and size of lysosomes. Some of the vacuoles contained vesicle like structures. Although there was no impairment of spermatogenesis, the changes in the Sertoli cells may lead to changes in spermatogenesis after chronic exposure.

Administration, Oral↗

Selective embolization of internal iliac artery for massive haemorrhage from bladder secondary to carcinoma.

Uncontrolled haemorrhage from the urinary bladder secondary to carcinoma can at times be a life-threatening complication. We report a case of recurrent carcinoma of bladder where all the conservative measures for controlling hematuria had failed. Selective embolization of both internal iliac arteries was undertaken which controlled haematuria within 12 hours of the procedure. The procedure had not caused any complication up until the patient was last seen 5 months after the procedure.

Carcinoma, Transitional Cell↗

Value and limitations of secondary femoropopliteal bypasses with polytetrafluoroethylene.

Secondary femoropopliteal bypasses with polytetrafluoroethylene (PTFE) grafts are widely regarded to be of questionable value. This has prompted some to abandon all attempts at secondary revascularization with PTFE and others to recommend that primary femoropopliteal bypasses be performed preferentially with PTFE grafts so that vein may be used for secondary procedures. Because we questioned both of these views, we reviewed all femoropopliteal bypasses done at our institution in the past 12 years and identified 73 secondary PTFE femoropopliteal procedures performed after a failed ipsilateral infrainguinal bypass (69 failed femoropopliteal; 4 failed femorodistal). Seventy (96%) secondary bypasses were performed for limb salvage and 3 (4%) for severe disabling claudication. Insertion of grafts to the popliteal artery was above the knee in 26 (36%) and below the knee in 47 (64%). Primary life-table graft patency at 4 years was only 38%. Forty-eight reinterventions in 34 limbs were required to restore or maintain graft patency in thrombosed or failing grafts. For thrombosed grafts, 20 interventions consisted of 9 simple thrombectomies and 11 thrombectomies with additional revision procedures (5 distal or proximal extensions, 6 patch angioplasties). Twenty-eight lesions threatening graft patency were treated by percutaneous transluminal angioplasty in 3, proximal or distal extensions in 20, and patch angioplasty in 5. As a result of these reinterventions, the overall secondary patency rate was 55% at 4 years, and the limb salvage rate was 74% at 4 years. Although aggressive follow-up and reintervention may be required, the use of secondary PTFE conduits in the femoropopliteal position is a viable option in patients undergoing limb salvage procedures who are at high risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗