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Biomedical subjects

A Joshi

Publications and source records attributed to A Joshi.

At least 19 recordsLinked to original sources
PubMed2026

Reduced Length of ADT and ARTA With XRT in High-Risk Prostate Cancer (RELAX): A Randomised Controlled Trial.

AIM: To assess the efficacy of a short, intensified regimen of androgen deprivation therapy (ADT) and androgen receptor-targeted agent (ARTA) with curative-intent external beam radiotherapy (XRT) for high-risk prostate cancer (HRPCa) staged with prostate specific membrane antigen (PSMA) imaging. MATERIALS AND METHODS: The RELAX (Reduced Length of ADT and ARTA with XRT in high-risk prostate cancer) trial is a multicentre, phase II randomised non-inferiority trial comparing 9 months of ADT and 6 months of ARTA against the standard 24-month ADT, with definitive dose-escalated hypofractionated pelvic radiotherapy for PSMA-staged non-metastatic HRPCa. The primary endpoint is 5-year disease-free survival (DFS), defined from randomisation to first biochemical or clinico-radiological recurrence or any-cause death. Secondary endpoints include biochemical failure-free survival, metastasis-free survival, overall survival, testosterone recovery, treatment-related adverse effects, and patient-reported outcomes. Participants are monitored with serial serum PSA and testosterone levels, CTCAE and PRO-CTCAE assessments, and PSMA-PETCT at recurrence. The non-inferiority margin is set at 10% absolute difference from an expected 5-year DFS of 85% in the standard arm, with intention-to-treat analysis. The trial is ethics board approved and funded by institutional intramural grant, and registered on clinicaltrials.gov (NCT06818682). RESULTS: The planned accrual of 206 participants commenced in February 2025, with nearly a third of enrolment completed till date. CONCLUSION: The RELAX trial incorporates contemporary standards of PSMA-based staging, dose-escalated hypofractionated radiotherapy, and ARTA for HRPCa. The results are expected to inform the efficacy of a shorter, intensified androgen suppression strategy against the prevailing standard of long-term ADT for these patients.

Humans↗
PubMed1992

Crossed renal ectopia with pelvic lipomatosis: a new syndrome involving chromosome 1.

An 18-year-old male patient is described who possesses both kidneys on one side (crossed renal ectopia), together with pelvic lipomatosis. In general, lipomatosis is benign, but here the tissue shows the rare feature of malignancy. Chromosomally, the patient is typically characterised by somatic translocations involving chromosome 1 (37% metaphases); these almost always exhibit a whole chromosome translocation with chromosome 6 (35%), although involvement of chromosome 1 with chromosome 8 is present in 2% of metaphases. Other chromosomal features encountered in Giemsa-stained and G-banded preparations from lymphocyte cultures include the prevalence of a small Y chromosome in 25% of metaphases, the presence of marker dots in 20%, and acrocentric associations in 8%-10% of metaphases. However, more than 50% of metaphases have a normal 46XY karyotype with a normal-sized Y-chromosome. Crossed renal ectopia with pelvic lipomatosis can therefore be assigned to a new syndrome characterised by a whole-chromosome translocation involving chromosomes 1 and 6.

Adolescent↗
PubMed1992

Multiple granular cell tumors of the gastrointestinal tract with subsequent development of esophageal squamous carcinoma.

A 52-year-old woman initially presented to our medical center with synchronous, submucosal tumors of the esophagus, stomach, and transverse colon. The gastric and colonic tumors were resected, and both displayed infiltrating sheets of polygonal cells with coarsely granular cytoplasm and small vesicular nuclei. The neoplastic cells of both tumors were immunoreactive for S-100 protein. Ultrastructural studies revealed the lysosomal nature of the cytoplasmic granules. Although the esophageal mass was not resected, it was felt that this represented another focus of granular cell tumor of the gastrointestinal tract. Two years later, she presented with disseminated squamous carcinoma of the esophagus. At autopsy, a submucosal granular cell tumor was found adjacent to the squamous carcinoma of the esophagus. To our knowledge, this is the first reported case of synchronous granular cell tumors that involved multiple segments of the gastrointestinal tract, one of which was later associated with a squamous carcinoma of the esophagus.

Carcinoma, Squamous Cell↗
PubMed1992

Mastoparan blockade of currents through Ca(2+)-activated K+ channels in bovine chromaffin cells.

The action of mastoparan (a wasp venom peptide) on "maxi" Ca(2+)-activated K+ channels was studied in excised inside-out patch recordings from cultured bovine chromaffin cells, under normal conditions (160 mM K+ inside, 154 mM Na+ outside). Mastoparan, when applied on the intracellular side of the membrane reduced the open channel probability in a concentration dependent manner. Changes in the channel kinetics were complex. The histograms of the open dwell times were all described by either one or two exponentials. Mastoparan shortened the mean duration of the major (long) component and to a lesser extent the minor (short) component. Closed dwell times, were described by three exponentials. While the short (major) component was prolonged by mastoparan, and the intermediate component was unaffected, the long component was shortened. Overall mean closed times were prolonged. The changes in channel kinetics could only partly be explained by a channel-blocking mechanism, even when assuming that mastoparan acts as both an intermediate and a slow channel blocker suggesting that it affects gating mechanism. The fact that mastoparan is a calmodulin inhibitor and a G-protein activator raises the possibility that in bovine chromaffin cells, either the membrane-bound calmodulin or a G-protein, plays a role in the modulation of Ca(2+)-activated K+ channels.

Animals↗
PubMed1992

Improving dental epidemiologic data collection with computers.

A computerized dental data recording system (DDRS) was developed for the New England Elder Dental Study to improve data quality and increase field staff efficiency. The DDRS displays video screens similar to traditional paper forms to record data on coronal and root caries, dentate and denture status, subacute bacterial endocarditis screening, gingival bleeding, calculus, and periodontal attachment level. DDRS provides facilities for date and exam-component time tracking, on-line contextual comments, random record retrieval, editing, data backup, and data output in various data formats. This study compared the DDRS with a paper-form system for data entry accuracy. Dental caries and periodontal disease measurement data from 38 subjects were recorded on paper forms and independently entered using DDRS. The DDRS identified 150 illogical data errors, 39 inconsistent data errors, 7 invalid data and 34 miscellaneous data errors. Four technicians with field experience using both paper forms and DDRS reported time savings using DDRS in the field. DDRS has the potential for additional time savings by minimizing the time for data coding, cleaning, and management. Results demonstrate that DDRS could improve the quality of oral epidemiologic data by mandating strict adherence to protocols, preventing errors, and increasing field efficiency.

Computers↗
PubMed1992

Prevalence and intraoral distribution of coronal and root caries in middle-aged and older adults.

This work describes the prevalence and intraoral distribution of coronal and root caries in 326 predominantly white, educated, middle-aged and older adults. Study participants were recruited from Tufts Geriatric Outreach Program, Nutritional Status Study (NSS), and the Forsyth Root Caries Study. Eighty-five percent of participants reported visiting their dentist in the last year. The median number of teeth was 21 in the 65+ age-group, and 40% of participants had coronal caries and 33% had root carious lesions. The mean coronal and root caries (DFS) was higher and the proportion of decayed surfaces to all decayed and filled surfaces (%D/DFS) was lower than in other comparable studies. A comparative analysis of intraoral distribution of coronal and root caries and their relation with age is discussed.

Adult↗
PubMed1991

Interaction of benzanthrone with cytochrome P450: altered patterns of hepatic xenobiotic metabolism in rats.

Benzanthrone, an anthraquinone dye intermediate, is commonly used for the synthesis of a number of polycyclic vat and disperse dyes. Our prior studies have shown that benzanthrone can be metabolized by rat hepatic microsomal cytochrome P450 (P450) (Biochem. Int., 18, 1989, 1237). In this study, the interaction of benzanthrone with rat hepatic microsomal P-450 and its effect on xenobiotic metabolism have been investigated. Parenteral administration of benzanthrone (40 mg/kg body weight) for 3, 7, or 21 days caused no change in the relative body weight or organ weight of rats. The levels of P450 were found to be reduced (33%-50%) in all the benzanthrone-exposed animals at all the time periods. In vitro addition of benzanthrone caused a spectral change with oxidized P450 and concentration-dependent reduction in the carbon monoxide spectrum of dithionite-reduced P450. The addition of benzanthrone to hepatic microsomes prepared from phenobarbital-treated rats resulted in spectral changes characterized by an absorbance maximum at 397 nm indicative of type I binding. In vitro addition of benzanthrone showed a concentration-dependent inhibition of hepatic aminopyrine N-demethylase (APD) and ethoxyresorufin-O-deethylase (ERD) activities with respective I50 values of 9.5 x 10(-4) and 8.0 x 10(-5) M. However, the inhibition of aryl hydrocarbon hydroxylase (AHH) even at the highest concentration of benzanthrone (10(-2) M), was of the order of only 29%. In vivo administration of benzanthrone also led to the inhibition of APD, AHH, and ERD activities at all treatment times although the magnitude of inhibition was of a lower order.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Penile cancer--the sentinel lymph node controversy.

The management of lymph nodes in penile cancer has always been a problem. Sentinel lymph node biopsy was supposed to solve this problem but has not been universally accepted due to conflicting results. We herein present a case of penile cancer with bilateral pathologically positive inguinal lymph nodes associated with concurrent negative sentinel lymph node biopsies. We discuss the possible reasons for this situation and suggest guidelines to study this issue.

Biopsy↗
PubMed1991

Pollution and sanitary quality of river Narmada in relation to human use at Mandla.

Study of physico-chemical characteristics and indicator bacterial population of Narmada river water at six different sites during summer, revealed extremely poor microbiological sanitary quality for human use. Free CO2 was found to be absent from all the sampling sites studied which indicates the trophogenic activity in the river water at Mandla. BOD value ranged from 1.0 to 2.5 mgl-1 and were less than the permissible limits of BOD in fresh waters i.e. 3-6 mgl-1.

Enterobacteriaceae↗
PubMed1991

The dominance of cyclic sliding in producing wear in total knee replacements.

From a literature survey, it was evident that a wide variety of kinematic conditions occur at the femoral-tibial bearing surfaces, including various degrees of rolling and sliding. A test machine was constructed to reproduce these conditions, applied to spherical-ended metal 'femoral' components acting on a flat polyethylene 'tibial' plateau. The load was cyclic at 2.2 kN for 10 million cycles with distilled water lubricant. For cyclic load only, a shiny depression was formed. With oscillating and sliding superimposed, there was severe surface and subsurface cracking resulting in high wear. When rolling motion was applied, a shiny wear track was formed with minimal cracking and wear. Such surface phenomena were observed in retrieved knee specimens, probably reflecting the kinematics associated with the knee. Low-conformity components inserted with high ligamentous laxity are susceptible to anteroposterior sliding and hence high wear. More-conforming components are less susceptible to wear because they limit sliding as well as reduce contact stresses.

Corrosion↗
PubMed1979

Is the injection of DNA enough to cause bacteriophage P22-induced changes in the cellular transport process of Salmonella typhimurium?

It was demonstrated earlier in this laboratory that phage P22 induces a transient depression in the cellular transport processes of the host Salmonella typhimurium immediately after infection and that an effective injection process is enough to cause the depression. By using defective phage particles that contain host DNA instead of phage DNA for infection, it has been demonstrated that the injection of phage-specific DNA is essential for this. The defective particles adsorbed to the host and injected their DNA, but the cellular transport processes of the host were not altered. Thus, the injection of host DNA by the phage fails to affect the transport process. Insensitivity of the phage DNA-induced depression in transport to chloramphenicol rules out the involvement of newly synthesized protein in this change and indirectly suggests the possible role of phage DNA-associated internal proteins of P22.

DNA, Viral↗
PubMed1978

E.s.r. of spin-trapped radicals in aqueous solutions of peptides. Reactions of the hydroxyl radical.

The reactions of hydroxyl radicals with 30 dipeptides and several larger peptides were studied in aqueous solutions. The OH radicals were generated by U.V. photolysis of H2O2. The short-lived peptide radicals were spin-trapped using t-nitrosobutane and identified by e.s.r. For dipeptides containing the amino terminal residues glycine, alanine and phenylalanine, abstraction of the hydrogen from the carbon adjacent to the peptide nitrogen was the major process leading to the spin-adducts. Such radicals will be referred to as backbone radicals. Dipeptides with a carbonyl terminal serine residue and also glycylglutamic acid form both backbone and side-chain radicals, with the latter being formed in larger quantities. For dipeptides, side-chain radicals were detected on either the carboxyl or amino terminal residues of both. The effect of pD on the e.s.r. sectrum of the spin-adducts of glycylglycine was studied and the pK of the carboxyl group of this radical was determined to be 2.5. For (Ala)3 and (Ala)n, with an average value of n = 1800, backbone and minor side-chain radicals were observed. For ribonucleases-S-peptide, containing 20 amino acid residues, both backbone and side-chain radicals were detected.

Dipeptides↗
PubMed1978

E.s.r. study of the post-radiolysis growth of spin-trapped radicals in gamma-irradiated aqueous solutions of thymine.

The post-irradiation growth of the spin-adduct nitroxide radical produced by the addition of the thymine--OD radical to t-nitrosobutane (tNB) in gamma-irradiated, de-aerated D2O solutions was investigated by e.s.r. The thymine--OD radical was formed by the addition of an OD radical to the C(5) position of thymine. Growth reached a greater maximum value and was more rapid with increasing dose. At a fixed dose, growth was also greater and more rapid if oxygen was present after gamma-radiolysis. The addition of a second radical to the spin-adduct nitroxide during radiolysis to give a diamagnetic intermediate, which can regenerate the spin-adduct radical during storage in air-free and in air-saturated solutions at room temperature, was inferred to be responsible for post-irradiation growth. U.V. photolysis at 260-280 nm of a solution containing the diamagnetic intermediate rapidly regenerates the spin-adduct nitroxide. The longer lifetime of the diamagnetic intermediate in oxygen-free solutions may be relevant to an understanding of the anoxic sensitization by nitroxides in cellular systems.

Cyclic N-Oxides↗
PubMed1977

Cyanamide mediated syntheses under plausible primitive earth conditions. II. The polymerization of deoxythymidine 5'-triphosphate.

When an aqueous solution (pH 7.0) of 3H deoxythymidine 5'-triphosphate, deoxythymidine 5'-phosphate, 4-amino-5-imidazolecarboxamide, cyanamide and ammonium chloride was dried and heated at 60 degrees C for 18 h, oligomers were obtained in a yield of approximately 80%. After the chemical degradation of any pyrophosphate bonds present in these oligomers, linear polynucleotides of up to 7-8 units in length were isolated by DEAE cellulose column chromatography and identified by enzymatic digestion procedures. The di- and trinucleotide fractions were degraded 87% and 100% by snake venom phosphodiesterase and 39% and 9% by spleen phosphodiesterase. This synthesis of deoxythymidine oligonucleotides was conducted under potentially prebiotic conditions and may offer a possible method for the synthesis of deoxyoligonucleotides on the primitive Earth.

Aminoimidazole Carboxamide↗
PubMed1977

E.s.r. of spin-trapped radicals in aqueous solutions of amino acids. Reactions of the hydroxyl radical.

The radicals produced by reactions of hydroxyl radicals with amino acids in aqueous solutions have been investigated. Hydroxyl radicals were formed by U.V.-photolysis of hydrogen peroxide and the short-lived amino acid radicals were spin-trapped by tert-nitrosobutane and identified by electron spin resonance spectroscopy. Nineteen amino acids were studied, and several radicals were identified which have not been observed previously by other methods. Only side-chain radicals were identified for alanine, threonine, aspartic acid, asparagine, lysine, phenylalanine, tyrosine, proline and hydroxyproline; whereas for glycine the C(2) carbon radical was spin-trapped. Both C(2) carbon radicals and side-chain radicals were assigned to valine, leucine, isoleucine, serine, glutamic acid, glutamine, arginine and methionine.

Amino Acids↗
PubMed1977

E.s.r. of spin-trapped radicals in aqueous solutions of amino acids. Reactions of the hydrated electron.

The reactions of hydrated electrons (eaq-) with amino acids were investigated by the spin-trapping method and by electron spin resonance. Tertiary nitrosobutane was used as a spin-trap to stabilize the short-lived radicals. Hydrated electrons were produced by gamma-radiolysis of de-aerated aqueous solutions of amino acids in the presence of sodium formate or tertiary butanol to scavenge OH. Radicals produced by reductive deamination of 19 amino acids were identified. Radicals formed by scission of the CH3-S- and -S-CH2- bonds of methionine as well as by deamination were observed. In the case of phenylalanine the radical formed by electron addition followed by proton transfer was identified. The reaction of proline and of hydroxyproline with eaq- resulted in the opening of the cyclic structure.

Amino Acids↗