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P Balagopal

Publications and source records attributed to P Balagopal.

10 recordsLinked to original sources
PubMed1998

Age-related sarcopenia in humans is associated with reduced synthetic rates of specific muscle proteins.

Sarcopenia of aging is not explained entirely on the basis of age-associated reduced physical activity. Progressive neuromuscular changes and diminishing anabolic hormone levels are thought to contribute to the pathogenesis of sarcopenia. Decline in muscle mass indicates a decline in muscle protein content. Recent studies demonstrated an age-related decline in synthesis rate of mixed muscle proteins, myosin heavy chain and mitochondrial protein. Reductions in myosin heavy chain and mitochondrial protein synthesis rates have been correlated with age-associated decrements in muscle strength and aerobic exercise tolerance, respectively. These changes have been reported as early as 50 y of age and are related to the decline in insulin-like growth factor (IGF)-I, testosterone and dehydroepiandrosterone (DHEA)-sulfate. The declining ability to remodel these important muscle proteins may therefore play a role in the development of muscle wasting, metabolic abnormalities and impaired physical functioning seen in old age.

Aging↗
PubMed1998

PCR-ELISA for the early diagnosis of invasive pulmonary aspergillus infection in neutropenic patients.

AIM: To evaluate a newly developed aspergillus mitochondrial gene PCR-ELISA assay for the early diagnosis of invasive pulmonary aspergillosis (IPA) in neutropenic patients. METHODS: The aspergillus mitochondrial gene was chosen for the amplification target for use with a solution hybridisation assay with colorimetric end stage detection in microtitre plate format (PCR-ELISA). The study group comprised neutropenic patients undergoing febrile episodes not responding to standard antibacterial antibiotics. Patients underwent computed tomography and bronchoscopy. Bronchoalveolar lavage (BAL) fluids were examined by culture and PCR. RESULTS: The aspergillus mitochondrial gene PCR-ELISA was both sensitive (100%) and specific (100%) for IPA in neutropenic patients. All 12 patients with definite or probable IPA had PCR positive BAL fluids. None of the patients with undiagnosed or confirmed infections of other aetiologies were mitochondrial PCR positive. Speciation based upon amplicon size difference was possible. CONCLUSIONS: Aspergillus mitochondrial DNA PCR-ELISA on BAL fluid is useful in the early diagnosis of IPA in neutropenic patients alone or, potentially, as an indication for thoracic computed tomography.

Adolescent↗
PubMed1997

Skeletal muscle myosin heavy-chain synthesis rate in healthy humans.

Mixed muscle protein synthetic rate has been measured in humans. These measurements represent the average of synthetic rates of all muscle proteins with variable rates. We determined to what extent the synthesis rate of mixed muscle protein in humans reflects that of myosin heavy chain (MHC), the main contractile protein responsible for the conversion of ATP to mechanical energy as muscle contraction. Fractional synthetic rates of MHC and mixed muscle protein were measured from the increment of [13C]leucine in these proteins in vastus lateralis biopsy samples taken at 5 and 10 h during a primed continuous infusion of L-[1-13C]leucine in 10 young healthy subjects. Calculations were done by use of plasma [13C]ketoisocaproate (KIC) and muscle tissue fluid [13C]leucine as surrogate measures of leucyl-tRNA. Fractional synthetic rate of MHC with plasma KIC (0.0299 +/- 0.0043%/h) and tissue fluid leucine (0.0443 +/- 0.0056%/h) were only 72 +/- 3% of that of mixed muscle protein (0.0408 +/- 0.0032 and 0.0603 +/- 0.0059%/h, respectively, with KIC and tissue fluid leucine). Contribution of MHC (7 +/- 1 mg.kg-1.h-1) to synthetic rates of whole body mixed muscle protein (36 +/- 5 mg.kg-1.h-1) and whole body protein (127 +/- 4 mg.kg-1.h-1) is only 18 +/- 1 and 5 +/- 1%, respectively. This relatively low contribution of MHC to whole body and mixed muscle protein synthesis warrants direct measurement of synthesis rate of MHC in conditions involving abnormalities of muscle contractile function.

Adult↗
PubMed1997

Effects of aging on in vivo synthesis of skeletal muscle myosin heavy-chain and sarcoplasmic protein in humans.

A decline in muscle mass and contractile function are prominent features of the sarcopenia of old age. Because myosin heavy chain is an important contractile protein, it was hypothesized that synthesis of this protein decreases in sarcopenia. The fractional synthesis rate of myosin heavy chain was measured simultaneously with rates of mixed muscle and sarcoplasmic proteins from the increment of [13C]leucine in these proteins purified from serial needle biopsy samples taken from 24 subjects (age: from 20 to 92 yr) during a primed continuous infusion of L-[1-(13)C]leucine. A decline in synthesis rate of mixed muscle protein (P < 0.01) and whole body protein (P < 0.01) was observed from young to middle age with no further change with advancing age. An age-related decline of myosin heavy-chain synthesis rate was also observed (P < 0.01), with progressive decline occurring from young, through middle, to old age. However, sarcoplasmic protein synthesis did not decline with age. Myosin heavy-chain synthesis rate was correlated with measures of muscle strength (P < 0.05), circulating insulin-like growth factor I (P < 0.01), and dehydroepiandrosterone sulfate (P < 0.05) in men and women and free testosterone levels in men (P < 0.01). A decline in the synthesis rate of myosin heavy chain implies a decreased ability to remodel this important muscle contractile protein and likely contributes to the declining muscle mass and contractile function in the elderly.

Adult↗
PubMed1997

Skeletal muscle myosin heavy chain synthesis in type 1 diabetes.

Although insulin's anticatabolic effect on protein metabolism in type 1 diabetes has been clearly shown to be related to the inhibition of protein breakdown, insulin's effect on muscle protein synthesis remains controversial. Cross-limb studies and measurements of synthesis rates of mixed muscle protein have yielded conflicting results. These measurements represent the mean synthesis of several muscle proteins and may miss changes in the synthesis rates of individual muscle proteins. We measured the fractional synthesis rates of myosin heavy chain (MHC), the principal muscle contractile protein, and mixed muscle protein (MMP) in six type 1 diabetic patients during insulin deprivation and insulin treatment. Comparisons were made with six healthy control subjects. Muscle biopsies were taken at 2 h and 8 h during a primed continuous infusion of L-[1-13C]leucine. MHC was purified by a preparative continuous elution gel electrophoresis, and fractional synthesis rates were calculated. We found that in type 1 diabetic subjects, the fractional synthesis rates of MHC and MMP during insulin treatment are similar to those of control subjects. Acute insulin deprivation did not affect either the synthesis rate or the ratio of MHC to MMP in type 1 diabetic subjects. In the postabsorptive state, acute insulin deprivation has no effect on MHC or MMP synthesis in type 1 diabetic patients.

Adult↗
PubMed1996

Mass spectrometric methods for determination of [13C]Leucine enrichment in human muscle protein.

Two modified GC-based isotope ratio MS (IRMS) techniques, for measurement of [13C]leucine enrichment in muscle protein, were compared with a conventional dual inlet technique. Of these three, two involved HPLC purification of leucine and liberation of carbon dioxide (CO2) using the ninhydrin reaction. In the conventional technique the CO2 was introduced into the MS by a dual inlet system following cryogenic concentration. In the second method (ninhydrin/GC/IRMS) the CO2 was purified by on-line GC. In the third technique, GC/combustion/IRMS, derivatized amino acids are separated by GC and analyzed after combustion. A primed continuous infusion of L-[1-13C]leucine was given intravenously to human subjects and needle quadriceps muscle biopsies were taken to measure [13C]leucine enrichment in muscle protein. All three methods demonstrated excellent correlation (r > 0. 999). Differences in the measurement of [13C]leucine enrichment in muscle protein were <6%. The ninhydrin techniques require microgram quantities of leucine, with the conventional technique requiring twice the amount as the ninhydrin/GC/IRMS method. The GC/combustion/IRMS technique requires only nanogram quantities of leucine with similar precision enabling measurement of synthesis rates of individual proteins from biopsy samples. We have measured the isotopic enrichment of myosin heavy chain and mixed muscle protein in human subjects using the GC/combustion/IRMS technique.

Calibration↗
PubMed1996

Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men--a clinical research center study.

Testosterone replacement in hypogonadism has long been known to promote nitrogen retention and increase body density, but the mechanisms of nitrogen retention and body composition changes are poorly defined. We measured body composition and muscle protein synthesis in five hypogonadal men before and 6 months after initiating testosterone replacement. Body composition was examined using dual energy X-ray absorptiometry. Muscle mass was estimated both by excretion of creatinine on a meat-free diet and from appendicular mass measured using dual energy X-ray absorptiometry. Muscle protein synthesis was assessed by measuring the increment of [13C]leucine in mixed muscle protein and myosin heavy chain during a continuous infusion of L-[l-13C]leucine. In all subjects there was an increase in fat-free mass (average, 15%; range, 10-22%; P = 0.02) and a decrease in fat mass (-11%; range, -0.4% to -22.0%; P = 0.03). Muscle mass also increased in everybody (mean, 20%; range, 11-32%; P = 0.04) such that 65% of the increase in fat-free mass could be attributed to accretion of muscle. The accumulation of muscle was associated with a 56% (P = 0.015) increase in the fractional synthesis rate of mixed skeletal muscle proteins and a trend toward a similar increase in the fractional synthesis rate of myosin heavy chain (46%; P = 0.098). We conclude that testosterone replacement in hypogonadal men enhanced skeletal muscle mass by stimulating the muscle protein synthesis rate.

Amino Acids↗
PubMed1994

Isolation of myosin heavy chain from small skeletal muscle samples by preparative continuous elution gel electrophoresis: application to measurement of synthesis rate in human and animal tissue.

A convenient procedure for the isolation of milligram quantities of myosin heavy chain (MHC) from small samples of muscle tissue using preparative gel electrophoresis is described. Application of the methodology to measurements of the fractional synthesis rates (ks) of MHC using skeletal muscle biopsy samples from humans and cardiac tissue from pigs following continuous intravenous infusions of stable isotope (L-[1-13C]-leucine) is demonstrated. The sensitivity and reproducibility of the determination of stable isotope enrichment are also defined. In addition, measurements of the ks of MHC in skeletal muscle of rats in vivo using radioisotope-tracer methodologies are described.

Animals↗