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R Nath

Publications and source records attributed to R Nath.

At least 109 records · Page 6Linked to original sources
PubMed1997

Application of AAPM Radiation Therapy Committee Task Group 23 test package for comparison of two treatment planning systems for photon external beam radiotherapy.

Task Group 23 of the AAPM Radiation Therapy Committee has produced a test package for verification of the accuracy of treatment planning for photon external beam therapy. The package includes measured fundamental beam data for 4 and 18 MV x rays, and 13 test cases with measured dose values at selected points, which serve as the reference for determination of calculated dose accuracy. Test cases include three square fields, two rectangular fields, a wedged field, a blocked field, and an irregular field, as well as cases of an off-center plane, source-to-SOURCE distance (SSD) variation, oblique incidence, and lung and bone inhomogeneities. This package was used to evaluate two treatment planning systems. Although average dose variations in most cases were less than 1%, maximum deviations up to 19% were observed in one planning system and up to 11% in the other. Dose deviations greater than 3% were observed for 51 of 532 points (in the 4 MV case) and for 124 of 586 points (in the 18 MV case). An additional component of the test package is an evaluation of radiological field width at different depths. The largest deviation for width was 17.4 mm for 4 MV and 9.1 mm for 18 MV. In 20% of the widths studied, the deviation observed was greater than 3 mm for the 4 MV case. In the 18 MV case 18% of the widths had deviations greater than 3 mm. Our data indicate that the accuracy of the two treatment planning systems tested here warrants improvement, even for simple treatment geometries involving photon beams, which are generally considered to be well understood. As one of the treatment planning systems is widely used in the US, it is concluded that the accuracy of the currently available commercial treatment planning systems is not adequate for achieving the generally stated goal of +/- 5% accuracy of dose delivery in radiation therapy. The AAPM Task Group 23 test package provides an extremely useful tool for a quantitative analysis of treatment planning systems for photon beam radiation therapy.

Humans↗
PubMed1996

Effects of ICE-like protease and calpain inhibitors on neuronal apoptosis.

Both ice-like protease and calpain have been shown to be involved in apoptosis in non-neuronal cells. Cultured rat cerebellar granule neurons undergo apoptosis when exposed to low potassium-containing medium. Calpain inhibitors 3-(4-iodophenyl)-2-mercapto-(Z)-2-propenoic acid (PD150606) and N-acetyl-Leu-Leu-Met-CHO (calpain inhibitor II) as well as interleukin-beta 1 converting enzyme (ICE)-like protease inhibitor Z-Asp-CH2OC(O)-2,6-dichlorobenzene (Z-D-DCB) protect against such apoptotic death. They also reduce DNA laddering and the number of apoptotic nuclei. Staurosporine treatment also evokes apoptosis in human neuroblastoma SH-SY5Y. While Z-D-DCB is again anti-apoptotic, calpain inhibitors only provide modest effects in this model. Our results suggest that ICE-like protease plays a critical role in neuronal apoptosis whereas the contributions of calpain are more cell-type dependent.

Animals↗
PubMed1996

Non-erythroid alpha-spectrin breakdown by calpain and interleukin 1 beta-converting-enzyme-like protease(s) in apoptotic cells: contributory roles of both protease families in neuronal apoptosis.

The cytoskeletal protein non-erythroid alpha-spectrin is well documented as an endogenous calpain substrate, especially under pathophysiological conditions. In cell necrosis (e.g. maitotoxin-treated neuroblastoma SH-SY5Y cells), alpha-spectrin breakdown products (SBDPs) of 150 kDa and 145 kDa were produced by cellular calpains. In contrast, in neuronal cells undergoing apoptosis (cerebellar granule neurons subjected to low potassium and SH-SY5Y cells treated with staurosporine), an additional SBDP of 120 kDa was also observed. The formation of the 120 kDa SBDP was insensitive to calpain inhibitors but was completely blocked by an interleukin 1 beta-converting-enzyme (ICE)-like protease inhibitor, Z-Asp-CH2OC(O)-2,6-dichlorobenzene. Autolytic activation of both calpain and the ICE homologue CPP32 was also observed in apoptotic cells. alpha-Spectrin can also be cleaved in vitro by purified calpains to produce the SBDP doublet of 150/145 kDa and by ICE and ICE homologues [ICH-1, ICH-2 and CPP32(beta)] to produce a 150 kDa SBDP. In addition, CPP32 and ICE also produced a 120 kDa SBDP. Furthermore inhibition of either ICE-like protease(s) or calpain protects both granule neurons and SH-SY5Y cells against apoptosis. Our results suggest that both protease families participate in the expression of neuronal apoptosis.

Amino Acid Sequence↗
PubMed1996

Maitotoxin induces calpain activation in SH-SY5Y neuroblastoma cells and cerebrocortical cultures.

Maitotoxin (MTX) is a highly potent marine toxin that activates both voltage-sensitive and receptor-operated calcium channels in the plasma membrane. This results in calcium overload that rapidly leads to cell death. We now report that maitotoxin (0.1-1 nM) induces calpain activation in both SH-SY5Y neuroblastoma cells and fetal rat cerebrocortical cultures. MTX-induced calpain activation was confirmed by the presence of autolytic fragmentation of both subunits of calpain. Secondly, the formation of calpain-produced alpha-spectrin breakdown products (150 and 145 kDa) was observed. We were also able to detect intracellular hydrolysis of a peptide substrate (succinyl-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin) by activated calpain in MTX-treated cells. Calpain inhibitors (calpain inhibitor I, MDL28170 and PD150606) inhibited spectrin breakdown and SLLVY-AMC hydrolysis in MTX-treated SY5Y cells. Our results suggest that (i) calpain is activated as a result of the maitotoxin-induced calcium influx; and (ii) coupling with the in situ calpain assays, maitotoxin would be a useful tool in investigating the physiologic and pathophysiologic roles of calpain in neuronal cells.

Amino Acid Sequence↗
PubMed1996

An alpha-mercaptoacrylic acid derivative is a selective nonpeptide cell-permeable calpain inhibitor and is neuroprotective.

Overactivation of calcium-activated neutral protease (calpain) has been implicated in the pathophysiology of several degenerative conditions, including stroke, myocardial ischemia, neuromuscular degeneration, and cataract formation. Alpha-mercaptoacrylate derivatives (exemplified by PD150606), with potent and selective inhibitory actions against calpain, have been identified. PD150606 exhibits the following characteristics: (i) Ki values for mu- and m-calpains of 0.21 microM and 0.37 microM, respectively, (ii) high specificity for calpains relative to other proteases, (iii) uncompetitive inhibition with respect to substrate, and (iv) it does not shield calpain against inactivation by the active-site inhibitor trans-(epoxysuccinyl)-L-leucyl-amido-3-methylbutane, suggesting a nonactive site action for PD150606. The recombinant calcium-binding domain from each of the large or small subunits of mu-calpain was found to interact with PD150606. In low micromolar range, PD15O6O6 inhibited calpain activity in two intact cell systems. The neuroprotective effects of this class of compound were also demonstrated by the ability of PD150606 to attenuate hypoxic/hypoglycemic injury to cerebrocortical neurons in culture and excitotoxic injury to Purkinje cells in cerebellar slices.

Acrylates↗
PubMed1996

Molecular basis of pathophysiology of Indian childhood cirrhosis: role of nuclear copper accumulation in liver.

Indian Childhood Cirrhosis (ICC) is a disease of abnormal copper metabolism commonly characterized by swelling and degeneration of liver cells along with the presence of orcein staining deposits of copper. Hepatic copper content of ICC patients was about 43 fold higher than those of control subjects. The data on sub-cellular distribution of copper revealed massive accumulation of Copper (73%) of total cell copper) in the nuclear fraction (455 micrograms Cu/g tissue nuclei). On further distribution of copper in nuclear fraction, the enrichment of copper in heterochromatin and euchromatin of ICC nuclei was found to be 48 and 15 fold higher over control fractions respectively. The ultra-violet spectra of heterochromatin and euchromatin isolated from ICC nuclear fraction showed a broad absorption maxima as compared to controls. Further, A260/A280 ratio was markedly lower in heterochromatin and euchromatin of ICC liver in comparison to controls. An antioxidant enzyme, catalase activity was also significantly reduced in ICC liver as compared to control. Further, DNA fragmentation studies indicated that there was significantly increased DNA fragmentation in ICC liver. Collectively, these findings suggest that massive accumulation of copper in nucleus and decrease in catalase activity was associated with DNA fragmentation in hepatocyte of ICC disease.

Catalase↗
PubMed1996

Apheresis in grade 4 bone marrow transplant associated thrombotic microangiopathy: a case series.

Bone marrow transplant-associated thrombotic microangiopathy (BMT-TM) ranges in severity from a self-limited to a fatal disorder. There has been no specific therapy for this condition. We have previously described a clinical grading system for BMT-TM, based upon lactate dehydrogenase level (LDH) and percentage fragmented cells (FC) as follows: grade 0, normal or increases LDH and % FC < or = to 1.2%; grade 1, normal LDH and FC > or = to 1.3%; grade 2, increases LDH and FC = 1.3-4.8%; grade 3, increases LDH and FC = 4.9-9.6%; and grade 4, increases LDH and FC > or = to 9.7%. Patients with grade 4 BMT-TM usually have fulminant disease and generally succumb. This study summarizes results using a variety of apheresis procedures in a series of 16 patients with grade 4 BMT-TM. The apheresis procedures consisted of plasma exchange (with replacement with fresh frozen plasma or cryo-poor plasma), and protein A immunoadsorption (PAI). The PAI exchanges were not done concurrently with plasma exchange procedures. Fifteen patients had undergone an allogeneic BMT and the 16th patient had undergone an autologous peripheral blood stem cell transplant. Half showed hematologic improvement with a downstaging of their TM to grades 1-3. All non-responders died a median of 11 days following the onset of grade 4 BMT-TM. The median survival in the responders was significantly (P = 0.001) increased to 218 days with three responders surviving more than 400 days following the onset of this severe complication. These results suggest a role for apheresis in the treatment of this lethal complication. Nevertheless grade 4 BMT-TM represents a major complication of BMT; the median survival in this group of 16 patients with grade 4 BMT-TM was only 31 days.

Adult↗
PubMed1996

Calculogenic potential of galactose and fructose in relation to urinary excretion of lithogenic substances in vitamin B6 deficient and control rats.

OBJECTIVE: Calculogenic potential of refined sugars galactose and fructose was examined in vitamin B6 deficient and control rats in terms of their capacity to increase urinary excretion of lithogens. METHODS: Male albino rats were fed vitamin B6 deficient diet with 51.7% sucrose+ starch or galactose or fructose as the source of carbohydrate. Pair-fed controls were maintained for all the groups for a period of four weeks. Twenty-four hour urine samples obtained at weekly intervals were analyzed for creatinine, calcium, oxalate, phosphate and uric acid. Microscopic urinalysis was performed at the end of the study. RESULTS: Urinary calcium excretion increased with respect to baseline in all groups except vitamin B6 control group. On day 28, galactose and fructose-fed rats demonstrated significant hypercalciuria as compared to the sucrose + starch fed group. Vitamin B6 deficient rats (irrespective of the sugar fed) excreted significantly greater urinary calcium compared to pair-fed controls. Oxalate excretion was significantly increased in rats fed galactose compared to those fed fructose or sucrose + starch. Vitamin B6 deficiency further increased oxalate excretion by 1.5, 1.9 and 1.7 fold in sucrose + starch, fructose or galactose fed animals, respectively. Urinary uric acid excretion was enhanced only in fructose-fed rats. There was no change in urinary excretion of creatinine and phosphate in different experimental and control groups. Increased urinary saturation with lithogens caused pronounced crystalluria in all the vitamin B6 deficient groups as well as galactose control group. CONCLUSION: The results suggest galactose ingestion is associated with a greater propensity to form calcium oxalate kidney stones than fructose. Calculogenic potential of galactose and fructose is further enhanced in vitamin B6 deficiency.

Animals↗
PubMed1996

Iatrogenic injury to the ilioinguinal and iliohypogastric nerves in the groin: a case report, diagnosis, and management.

A case of right-sided ilioinguinal and iliohypogastric neuralgia following laparoscopic repair in a 52-year-old man is presented. Significant pain persisted despite conservative measures and was successfully treated with resection of the ilioinguinal and iliohypogastric nerves in the retroperitoneal space. The anatomy, mechanisms of injury, and management of postherniorrhaphy neuropathy are reviewed.

Female↗
PubMed1996

Pilot study of combined cryosupernatant and protein A immunoadsorption exchange in the treatment of grade 3-4 bone marrow transplant-associated thrombotic microangiopathy.

Bone marrow transplant-associated thrombotic microangiopathy (BMT-TM) ranges in severity from a self-limiting to a fatal disorder. There is no specific therapy for this condition to date. We have previously described a simple clinical grading system (grade 0-4) for BMT-TM; patients with grade 3-4 BMT-TM do poorly. A previous study in our institution suggested that a combination of exchange with cryosupernatant replacement and protein-A immunoadsorption (PAI) might be of benefit. Therefore we performed a pilot study to evaluate the effectiveness of cryosupernatant alternating with PAI exchange for 2 weeks in a series of 13 patients with grade 3-4 BMT-TM. Twelve of 13 patients had undergone allogeneic-BMT a median of 25 days (range of 5-458 days) prior to the onset of grade 3-4 BMT-TM. The thirteenth patient had undergone autologous peripheral stem cell transplant 11 days prior to grade 4 BMT-TM. Pre-therapy, 10 patients had grade 4 BMT-TM and three had grade 3. Eight (62%) showed a response to treatment. Post-therapy, four responders had grade 3, three had grade 2 and one had grade 0 BMT-TM. The median follow-up of the responders is 90 days (range 21 to 464). Three responders have died at 21, 44, and 226 days following the development of BMT-TM of interstitial pneumonia in one, aspergillus in one, and multiorgan failure syndrome (MOFS) in one. The remaining responders are alive 66-465 days post-TM. All non-responders died of MOFS at 6-31 days post-TM. These results suggest that combined exchange with cryosupernatant alternating with PAI is effective therapy for some patients with moderate to severe BMT-TM and may improve survival.

Adult↗
PubMed1996

Role of epidural medication in the treatment of resistant low back pain.

Two hundred and eight patients of low back pain were studied in the department of orthopaedic surgery, GSVM Medical College, Kanpur. The patients were put on intensive conservative treatment in the form of analgesics, hard bed rest, spinal extension exercises, traction and lumbosacral support. Thirty-two patients did not respond to this treatment and their symptoms were of more than 6 months duration and they were subjected to epidural injection of local anaesthetic agent, saline and corticosteroids. The failed 6 cases were investigated for consideration of surgery. The aim of this study is to develop standardised strategy for the treatment of low back pain. For the low back pain patients not responding to intensive conservative treatment, an idea has been put forward in the form of epidural medication prior to considering them to surgery to prevent unnecessary incidence of "failed back". A trial of epidural injection is suggested to avoid surgery.

Adolescent↗
PubMed1995

Effect of beta-carotene on the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase in rat liver.

3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), is a rate-limiting enzyme in the biosynthesis of not only cholesterol but also a variety of non-sterol isoprenoids. It is subjected to multivalent feedback suppression by transcriptional and post-transcriptional control mechanisms mediated by sterols and non-sterol substances. In the present study, the effect of a plant isoprenoid, beta-carotene, on the expression of HMG-CoA reductase in rat liver was investigated. In control rats the hepatic levels of mRNA transcripts of HMG-CoA reductase increased following 2/3 partial hepatectomy with two peaks, one at 8 h and the other at 24 h. Administration of the carotenoid (70 mg/kg, given every alternate day for 3 consecutive weeks) partially inhibited the increase in the transcript level with a 50% reduction at 8 h and 30% reduction at 24 h post partial hepatectomy. Nuclear run-off assays with nuclei isolated from the resting liver and from livers of control rats and rats exposed to beta-carotene for 3 consecutive weeks and killed 8 h after partial hepatectomy indicated that beta-carotene did not inhibit the rate of transcription of HMG-CoA reductase gene. These observations suggest that beta-carotene regulates the expression of HMG-CoA reductase by some post-transcriptional mechanisms.

Animals↗
PubMed1995

Cadmium-induced nephrotoxicity in rhesus monkeys (Macaca mulatta) in relation to protein calorie malnutrition.

In this study, we compared results obtained in protein calorie malnourished (PCM) monkeys and controls given Cd2+ (5 mg Cd2+/kg body wt./day) orally for 24 weeks. After 16 weeks of Cd2+ exposure, an indolent renal failure develops in PCM monkeys which resulted in significant increase in urinary excretion of total protein, Cd2+, Zn2+ and Ca2+ as compared to corresponding to Cd(2+)-treated control group. In isolated proximal tubule brush border membrane vesicles (BBMV), Cd2+, Zn2+ and Ca2+ transport were significantly impaired in Cd(2+)-exposed PCM monkeys as compared to Cd(2+)-treated controls. The mechanism of higher urinary excretion of Cd2+, Zn2+ and Ca2+ was examined by analyzing the kinetic parameters of transport systems. The kinetic studies of Cd2+, Zn2+ and Ca2+ transport systems in the BBMV preparations of Cd(2+)-exposed PCM monkeys exhibited a significant decrease in Vmax and an appreciable increase in Km as compared to Cd(2+)-treated controls. These findings suggested that Cd2+ treatment of PCM monkeys caused either a decrease in the number of transporters in the brush border membrane or an increase in the number of less active transporters for Cd2+, Zn2+ and Ca2+. Furthermore, brush border membrane-bound enzymes, viz. alkaline phosphatase and leucine aminopeptidase, activities were significantly impaired in Cd(2+)-exposed PCM monkeys. Cadmium content in kidney cortex of Cd(2+)-exposed PCM monkeys was 3.34-fold higher than Cd(2+)-exposed controls. These findings also established that Cd2+ not bound to metallothionein (MT) was significantly higher in Cd-exposed PCM monkeys, which may be an important determinant in renal toxicity by interacting with sensitive sites in the renal cells and causing renal damage in Cd-exposed PCM monkeys.

Administration, Oral↗
PubMed1995

An evaluation of the recommendations of the TG-25 protocol for determination of depth dose curves for electron beams using ionization chambers.

AAPM Radiation Therapy Committee Task Group 25 has recently outlined a protocol for the determination of relative dose curves for electron beams [Med. Phys. 18, 73-109 (1991)]. We have performed an evaluation of this protocol by comparing the central axis depth dose curves determined from measurements using two different ionization chambers and three different phantom materials. Measurements were made with a Farmer-type PTW and Capintec ionization chamber in solid water, PMMA, and clear polystyrene phantoms irradiated by 6- and 15-MeV electron beams. Central axis depth dose curves were generated from the measured depth-ionization data using the new protocol. For both the chambers and energies investigated in this study, excellent agreement was observed among all the depth doses in water obtained from measurements in all of the three phantoms studied.

Electrons↗