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B Mittal

Publications and source records attributed to B Mittal.

At least 91 records · Page 5Linked to original sources

Effects of sequencing of the total course of combined hyperthermia and radiation on the RIF-1 murine tumor.

The optimal sequence for clinical utilization of combined radiotherapy and hyperthermia is not known. The clinical trials have resulted in similar responses whether hyperthermia is given before or after radiation. Moreover, studies addressing the best sequence for an entire course of multifractionated hyperthermia and radiation are lacking. In these experiments, the importance of sequencing of heat and irradiation in a multifractionated treatment regimen in RIF-1 murine tumors was studied. It was observed that a close sequence of heat and irradiation is more beneficial than separate cytotoxic action. When heat and irradiation were given simultaneously, (within 1 hour) 67% to 75% of the tumors were cured. Heat and irradiation given sequentially (the entire course of one following the entire course of the other, each separated by 72 hours) cured 20% of the tumors. No tumors were cured when treated with heat or irradiation alone. The tumor regrowth time (mean tumor doubling time) is much longer in simultaneous treatment than in sequential treatment. It appears that heating first decreases the effectiveness of subsequent irradiation, causing a shorter growth delay than the opposite sequence. Heat alone does not alter the tumor bed permanently, but irradiation seems to do so, resulting in a slower rate of growth upon recurrence.

Animals↗

Transglottic carcinoma.

The cases of 152 patients with transglottic carcinoma were reviewed. There were 31% T2, 39% T3, and 30% T4 lesions. Twenty-six percent of patients had neck node metastases at initial presentation, and 19% with no neck dissection or radical irradiation to the neck subsequently developed neck metastases. Patients treated with voice conservation surgery +/- neck dissection +/- radiation (VCS +/- ND +/- R) had small transglottic carcinomas, whereas total laryngectomy +/- neck dissection +/- radiation (TL +/- ND +/- R) was used for patients with larger lesions. The reason for radiation alone (RA) was the patient's poor general condition or refusal of surgery. The total failure rate (primary, neck, and distant metastases) was 39%. Patients treated with TL +/- ND +/- R had fewer primary and stomal failures (12%) than those treated by VCS +/- ND +/- R (23%) and RA (33%), but ultimate failure after salvage treatment was the same (12%-13%). Sixty percent of patients treated with VCS and 67% with RA had their voices preserved. The major complication rate (overall, 16%) was highest in the group treated with VCS +/- ND +/- R. Five-year observed and adjusted survival for the entire group was 47% and 55%, respectively. The lower survival in the RA group was attributable to a high death rate from intercurrent disease. The incidence of second tumors was 14%. Unfavorable prognostic factors were older age, pretreatment tracheostomy, advanced stage and the presence of tumor in surgical specimen, and lymph nodes.

Adult↗

Formation of myofibrils in spreading chick cardiac myocytes.

Cardiac myocytes were isolated from 5-6-day-old chick embryos and allowed to spread in culture. The distribution of alpha-actinin in the cells was followed for five days in culture by exposing permeabilized cells to rhodamine-labeled alpha-actinin and also by injecting the labeled alpha-actinin into living myocytes. In addition to labeling the Z bands of sarcomeres, the added alpha-actinin also labeled small particles that were usually arranged periodically in linear arrays with a spacing between particles of 0.3-2.0 micron. Actin was localized between the particles of alpha-actinin by means of fluorescein-labeled heavy meromyosin. The punctate localization of alpha-actinin was prominent in pseudopods, behind ruffles, and at the periphery of spreading cells. Long rows of particles of alpha-actinin were often parallel to one another with the alpha-actinin particles in register. These linear arrays appeared to merge laterally to form strands with broader concentrations of alpha-actinin. Other linear arrays were parallel to myofibrils in the cell and some extended outward from the ends of myofibrils. We conclude that during spreading of cardiac myocytes, myofibrils form at the cell periphery behind the extending margins of the cell, and that the aggregates of alpha-actinin found in these areas are nascent Z bands in the forming myofibrils.

Actinin↗

Analysis of myofibrillar structure and assembly using fluorescently labeled contractile proteins.

To study how contractile proteins become organized into sarcomeric units in striated muscle, we have exposed glycerinated myofibrils to fluorescently labeled actin, alpha-actinin, and tropomyosin. In this in vitro system, alpha-actinin bound to the Z-bands and the binding could not be saturated by prior addition of excess unlabeled alpha-actinin. Conditions known to prevent self-association of alpha-actinin, however, blocked the binding of fluorescently labeled alpha-actinin to Z-bands. When tropomyosin was removed from the myofibrils, alpha-actinin then added to the thin filaments as well as the Z-bands. Actin bound in a doublet pattern to the regions of the myosin filaments where there were free cross-bridges i.e., in that part of the A-band free of interdigitating native thin filaments but not in the center of the A-band which lacks cross-bridges. In the presence of 0.1-0.2 mM ATP, no actin binding occurred. When unlabeled alpha-actinin was added first to myofibrils and then labeled actin was added fluorescence occurred not in a doublet pattern but along the entire length of the myofibril. Tropomyosin did not bind to myofibrils unless the existing tropomyosin was first removed, in which case it added to the thin filaments in the l-band. Tropomyosin did bind, however, to the exogenously added tropomyosin-free actin that localizes as a doublet in the A-band. These results indicate that the alpha-actinin present in Z-bands of myofibrils is fully complexed with actin, but can bind exogenous alpha-actinin and, if actin is added subsequently, the exogenous alpha-actinin in the Z-band will bind the newly formed fluorescent actin filaments. Myofibrillar actin filaments did not increase in length when G-actin was present under polymerizing conditions, nor did they bind any added tropomyosin. These observations are discussed in terms of the structure and in vivo assembly of myofibrils.

Actinin↗

Interaction of fluorescently-labeled contractile proteins with the cytoskeleton in cell models.

To determine if a living cell is necessary for the incorporation of actin, alpha-actinin, and tropomyosin into the cytoskeleton, we have exposed cell models to fluorescently labeled contractile proteins. In this in vitro system, lissamine rhodamine-labeled actin bound to attachment plaques, ruffles, cleavage furrows and stress fibers, and the binding could not be blocked by prior exposure to unlabeled actin. Fluorescently labeled alpha-actinin also bound to ruffles, attachment plaques, cleavage furrows, and stress fibers. The periodicity of fluorescent alpha-actinin along stress fibers was wider in gerbil fibroma cells than it was in PtK2 cells. The fluorescent alpha-actinin binding in cell models could not be blocked by the prior addition of unlabeled alpha-actinin suggesting that alpha-actinin was binding to itself. While there was only slight binding of fluorescent tropomyosin to the cytoskeleton of interphase cells, there was stronger binding in furrow regions of models of dividing cells. The binding of fluorescently labeled tropomyosin could be blocked by prior exposure of the cell models to unlabeled tropomyosin. If unlabeled actin was permitted to polymerize in the stress fibers in cell models, fluorescently labeled tropomyosin stained the fibers. In contrast to the labeled contractile proteins, fluorescently labeled ovalbumin and BSA did not stain any elements of the cytoskeleton. Our results are discussed in terms of the structure and assembly of stress fibers and cleavage furrows.

Actinin↗

Comparative cost analysis of hemilaryngectomy and irradiation for early glottic carcinoma.

The cost of hemilaryngectomy (15 patients) was compared to that of radiation treatment (18 patients) in epidermoid carcinoma confined to the true vocal cord with normal mobility (T1N0). An average of $3,495 was saved if radiation therapy was chosen; savings in terms of working hours were also substantial. We maintain that, if different treatment methods yield the same cure rate and quality of life, then cost should be the next strong consideration in choosing a particular treatment method.

Carcinoma, Squamous Cell↗

Role of radiation in the management of early vocal cord carcinoma.

From 1952-1978, 177 patients with epidermoid carcinoma confined to the true vocal cords with normal mobility (T1NO) were treated with radiation alone. Five- and 10-year adjusted actuarial survival rates for all patients were 97 and 95%, respectively. The tumor recurred in the larynx and/or neck in 16% of patients with T1a (one cord involved) and 23% of the patients with T1b (both vocal cords involved) disease. Radiation failures were surgically salvaged in 89% of patients with T1a disease without anterior commissure involvement, in 60% of those with T1a disease with anterior commissure involvement and in 57% of those with T1b disease. Tumor was ultimately controlled in 97% of the patients with T1a and 90% of the patients with T1b disease. Voice was preserved in 93% of the patients with T1a disease and 77% of patients with T1b disease. Of 121 patients evaluated for voice quality, 77% had good and 22% had fair voice, while only one patient had poor quality of voice. Patients with fair or poor quality voice usually had had salvage hemilaryngectomy. We recommend radiation for all patients with early vocal cord carcinoma.

Adult↗

Non-Hodgkin's lymphoma of the stomach.

Thirty-seven patients with non-Hodgkin's lymphoma of the stomach were treated with curative intent by several single and combined modality regimens. Twenty-two patients presented with stage IE and 15 with stage IIE disease. All but three patients underwent laparotomy. Of all diagnostic procedures used, x-ray of the upper gastrointestinal tract proved to be most helpful in diagnosing malignant lesions (87%). Gastric cytology was suspicious or diagnostic of malignancy in 35% of the patients. Twelve of 34 evaluable patients (35%) developed recurrence. Distant metastases (75%) was the most common mode of failure. The recurrence rates varied by the type of therapy and also the extent of initial disease. Four of 12 patients (33%) were salvaged with retreatment. The 5-year actuarial no evidence of disease survival for the entire group was 61% (stage IE-57%; stage IIE-67%). Patients receiving combined modality therapy had significantly (p = less than 0.05) higher survival than patients treated with single modality treatment. Three of 29 patients (10%) died of surgical complications after gastrectomy. Radiation treatment was well tolerated. Our data and a critical review of the literature do not support the reportedly high incidence of gastric perforation after radiation treatment. We recommend the use of adjuvant radiation for stage IE and adjuvant radiation plus chemotherapy for stage IIE gastric lymphoma.

Adult↗

Induction of carnitine acetyltransferase by clofibrate in rat liver.

Administration of the anti-hypercholesterolaemic drug clofibrate to the rat increases the activity of carnitine acetyltransferase (acetyl-CoA-carnitine O-acetyltransferase, EC 2.3.1.7) in liver and kidney. The drug-mediated increase in enzyme activity in hepatic mitochondria shows a time lag during which the activity increases in the microsomal and peroxisomal fractions. The enzyme induced in the particulate fractions is identical with one normally present in mitochondria. The increase in enzyme activity is prevented by inhibitors of RNA and general protein synthesis. Mitochondrial protein-synthetic machinery does not appear to be involved in the process. Immunoprecipitation shows increased concentration of the enzyme protein in hepatic mitochondria isolated from drug-treated animals. In these animals, the rate of synthesis of the enzyme is increased 7-fold.

Acetyltransferases↗

Pure seminoma.

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Adolescent↗

Influence of clofibrate administration on the rate of synthesis of macromolecules in regenerating rat liver.

Administration of the antihypercholesterolaemic drug clofibrate stimulates the rates of synthesis of nucleic acids and proteins in rat liver. The biosynthesis of mitochondrial proteins also is enhanced by the drug. In drug-fed animals, the rates of incorporation in vivo of radioactive precursors into DNA, RNA and proteins are stimulated even when the liver undergoes regeneration following partial hepatectomy. The rate of synthesis of mitochondrial proteins in the regenerative phase is higher in clofibrate-fed animals. These effects are consistent with the hepatomegalic and mitochondria-proliferating property of the drug.

Animals↗

Purification of clofibrate-induced carnitine acetyltransferase from rat liver mitochondria.

The enzyme carnitine acetyltransferase (acetyl-CoA:carnitine O-acetyltransferase, EC 2.3.1.7) has been purified to homogeneity from hepatic mitochondria of clofibrate-fed rats. It is a protein of molecular weight 56 000 composed of two non-identical subunits of molecular weight 34 000 and 25 000. The enzyme is inhibited by palmityl-CoA as well as acetyl carnitine. The inhibition by fatty acyl-CoA is competitive with respect to both the substrates, carnitine and acetyl-CoA. The inhibition by acetylcarnitine is reversed by carnitine but not by acetyl-CoA.

Acetyl Coenzyme A↗

Effect of gamma-irradiation on cholesterol of chicken brain.

Cholesterol in chicken brain has been determined after head irradiation with 60Co gamma rays. The brain of five-week-old white Leghorn chickens, irradiated with 1200 R showed appreciable decrease in its cholesterol content after two and five days, and a slight increase after seven days of irradiation. But the cholesterol content after seven days of irradiation was still less than the control values. However, an insignificant increase in brain cholesterol (than control) was observed after 14 days of irradiation. Nine to ten weeks old Rhode Island Red chickens exposed to 4000 R head gamma-irradiation exhibited a similar effect in cholesterol content of the brain.

Animals↗

Genetic polymorphisms in GSTM1, GSTT1, GSTP1, GSTM3 and the susceptibility to gallbladder cancer in North India.

The glutathione S-transferase (GSTs) are polymorphic supergene family of detoxification enzymes that are involved in the metabolism of numerous potential carcinogens. Several allelic variants of polymorphic GSTs show impaired enzyme activity and are suspected to increase the susceptibility to various cancers. To find out the association of GST variants with risk of gallbladder cancer, the distribution of polymorphisms in the GST family of genes (GSTT1, GSTM1, GSTP1, and GSTM3) were studied in 106 cancer patients and 201 healthy controls. Genotypes were analysed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP). The frequencies of GSTM1 null and GSTM3*BB genotypes did not differ between patients and controls. The overall frequency of GSTT1 null was lower in cases as compared with controls (p=0.003, Odds ratio (OR) = 0.2, 95% confidence interval (CI), 0.1-0.6). After sex stratification, the GSTT1 null frequency was reduced only in female patients (p=0.008, OR = 0.2, 95% CI = 0.1-0.6). However, the GSTP1, ile/val genotype and the val allele were significantly higher in cases than controls (p=0.013, OR = 1.9, 95% CI = 1.1-3.1; p=0.027, OR = 1.5, 95% CI = 1.0-2.1), respectively. To study gene-gene interactions, a combined risk of gallbladder cancer due to ile/val or val/val were calculated in combination with null alleles of GSTM1 and GSTT1 or the *B allele of GSTM3, but there was no enhancement of risk. Gallstones were present in 57.5% of patients with gallbladder cancer, but there were no significant differences between allelic/genotype frequencies of the studied GST genes polymorphisms between patients with or without gallstones. To best of our knowledge, this is the first paper showing ile/val genotypes and val allele of GSTP1 to be associated with higher risk of gallbladder cancer.

Adult↗

Effect of antibiotics on Oxalobacter formigenes colonization of human gastrointestinal tract.

BACKGROUND AND PURPOSE: Oxalobacter formigenes is a bacterium residing in the human gastrointestinal tract that degrades oxalate and reduces its availability for absorption. This bacterium is assumed to be antibiotic sensitive, and repeated antibiotic therapies could eradicate it. The aim of the present study was to determine the differences in the colonization by O. formigenes of individuals who had been on antibiotics for at least 5 days at the time of sample collection and individuals who had not taken antibiotics for at least 3 months. PATIENTS AND METHODS: Stool samples were collected from 80 individuals without stone disease (35 with and 45 without antibiotic consumption) and 100 patients with stone disease (20 with and 80 without antibiotic consumption). Oxalobacter formigenes was detected by a polymerase chain reaction-based method, and the presence/absence of O. formigenes was correlated with urinary oxalate concentrations. RESULTS: Lower percentages of individuals without stone disease and with stone disease who were consuming antibiotics had O. formigenes colonization than individuals without antibiotic consumption. Urinary oxalate concentrations were higher in the individuals without O. formigenes than in colonized individuals. CONCLUSION: Our observations confirm a direct association between antibiotic consumption and absence of O. formigenes. Absence of intestinal O. formigenes could represent a pathogenic factor in calcium oxalate urolithiasis when antibiotics are prescribed generously.

Absorption↗