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Biomedical subjects

M Sun

Publications and source records attributed to M Sun.

At least 19 recordsLinked to original sources
PubMed1995

Site-directed mutagenesis of proteolytic antibody light chain.

Amino acid residues in a proteolytic antibody light chain selected by molecular modeling were substituted with Ala by site-directed mutagenesis. Hydrolysis of vasoactive intestinal polypeptide (VIP), the immunogen employed to elicit the antibody light chain, was reduced by > 95% by replacement of Ser27a or His93 by Ala residues. Similar reductions in the activity were observed using synthetic protease substrates containing Arg-methylcoumarinamide (MCA) and Lys-MCA bonds. Turnover of the Ser27a and His93 mutants was lower than that of wild-type protein by about two orders of magnitude. The activity of the wild-type protein was inhibited selectively by diisopropylfluorophosphate (DFP), a serine protease inhibitor, but the residual activity of the Ser26 mutant was refractory to DFP. The affinity of the wild-type light chain for the substrate ground state was nearly unaffected by mutations at Ser27a and His93. In contrast, a Ser26 single mutant and a His27d/Asp28 double mutant displayed increased Km (by about tenfold) and increased turnover (by about tenfold) using VIP as substrate. The kinetic constants for these mutants and the wild type protein were essentially identical with Boc-Glu-Ala-Arg as substrate. Thus, two types of residues participating in catalysis by the light chain have been identified. Ser27a and His93 are essential for catalysis but not for initial high affinity complexation and substrate. Ser26 and His27d or Asp28 participate in VIP binding and limit turnover indirectly.

Amino Acid Sequence↗
PubMed1995

Methodology for evaluating the incidence of second primary cancers with application to smoking-related cancers from the Surveillance, Epidemiology, and End Results (SEER) program.

The Surveillance, Epidemiology, and End Results (SEER) database is used to estimate the standardized incidence ratios (SIRs) of second primaries for all pairs of smoking-related cancers and to interpret the results in the context of our knowledge of the known effects of smoking on the incidence of each of the individual cancers. In evaluating the simultaneous incidence of two cancers, one must recognize the inherent duality of the two relevant SIRs linking the two cancers (e.g., A and B), namely, the SIRs of A following B and B following A. Under fairly general assumptions, the two SIRs are seen to be equal, and departures from equality suggest changes in risk status or the introduction of new risk factors after the incidence of the first primary. Based on these observations, a methodological strategy is developed. The data reveal several clear patterns. First, short-term incidence is uniformly much greater than long-term incidence. Second, the SIRs are consistently much higher for women than for men, for every pair of cancers studied. Third, the magnitudes of the SIRs are generally high and often substantially higher than would be expected on the basis of the known risks of smoking. Exceptionally high SIRs are observed between kidney and bladder cancer and between head and neck and esophageal cancer. Various influences may affect these high observed SIRs, including artifactual influences such as diagnostic, surveillance, and misclassification biases, and the effect of different exposure prevalences on subsequent SIRs, which may to some extent explain the strong sex differences. However, these artifacts do not appear to explain the magnitude of the observed SIRs, especially the very strong associations between kidney and bladder cancer and between head and neck and esophageal cancer. It seems likely that other factors play a role, including, possibly, host susceptibility factors or additional common risk factors other than smoking. Although multiple primary cancers are rare, they represent an especially fruitful population for detailed epidemiologic study.

Evaluation Studies as Topic↗
PubMed1995

Leptomeningeal tumor in primary central nervous system lymphoma: recognition, significance, and implications.

The true incidence of leptomeningeal tumor in primary central nervous system lymphoma is unknown. We studied prospectively the cerebrospinal fluid profile of 96 patients without acquired immunodeficiency syndrome but with primary central nervous system lymphoma at diagnosis, at completion of treatment, and at recurrence. Magnetic resonance images and pathology slides were examined for evidence of leptomeningeal tumor. Leptomeningeal tumor was diagnosed by (1) positive findings on cerebrospinal fluid cytology, (2) leptomeningeal or subependymal enhancement on magnetic resonance imaging, or (3) pathological evidence of leptomeningeal tumor. We recorded whether treatment directed against the leptomeninges was given. Cerebrospinal fluid was examined in 86 of 96 patients at diagnosis and 29 of 42 at recurrence. The incidence of leptomeningeal tumor was 42% at diagnosis and 41% at recurrence. Only elevated levels of protein and lactate dehydrogenase isoenzyme-5 were significantly associated with leptomeningeal tumor (p = 0.012, p = 0.016, respectively). Treatment against the leptomeninges was significantly associated with the probability of achieving a complete response and a longer freedom from relapse. Patients older than 50 years had a worse disease-specific survival but a similar probability of responding to therapy as younger patients. Our data show that leptomeningeal tumor in primary central nervous system lymphoma is more prevalent than originally thought, and indicate the need for therapy inclusive of the leptomeninges in all patients.

Arachnoid↗
PubMed1995

Action of organophosphate anticholinesterases on the three conformational states of nicotinic receptor.

Organophosphate and other ligands were examined for binding on the membrane-bond nicotinic receptor at three conformational states. Soman (pinacolyl methylphosphonofluoridate), sarin (isopropyl methylphosphonofluoridate, tabun (ethyl N-dimethylphosphoramidocyanidate) and phencyclidine did not show any effect on the binding of [25I]alpha-cobrotoxin to the nicotinic receptor. However, VX, O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothiolate, at concentrations higher than 10 umol/L exhibited profound inhibition on the equilibrium binding rates in a concentration-dependent manner. Agonist nicotine and antagonist d-tubocurarine also showed significant inhibitions.

Animals↗
PubMed1995

The change of carnitine content in seminal plasma after reversible injection occlusion of vas deferens.

The change in carnitine content in seminal plasma after reversible injection occlusion of vas deferens (RIOVD) was observed. RIOVD is a safe, effective and simple method of male fertility control. Carnitine was determined by microenzymatic method. The incidence of sperm disappearance increased with the duration of RIOVD and reached 90% at the end of 12 months after operation. Before RIOVD, the mean value of carnitine in seminal plasma was 336.9 +/- 78.1 nmol/ml (X +/- SD, n = 58); after RIOVD, the mean value of seminal plasma carnitine was 112.7 +/- 50.7 nmol/ml (n = 172) in the group with sperm disappearance, and 172.5 +/- 71.7 nmol/ml (n = 51) in the group without sperm disappearance. There was a significant difference in carnitine content between pre-operation and postoperation (p < 0.01). After RIOVD, the carnitine concentration in seminal plasma of the group with sperm disappearance was lower than that of the group without sperm disappearance (p < 0.01). The results suggest that carnitine content in seminal plasma following RIOVD may be a reference index for judging the success or failure of the operation.

Carnitine↗
PubMed1995

[Two autopsy cases of malignant mixed müllerian tumor of the uterus with metastasis to alimentary tract and liver].

Two autopsy cases (69 and 87-year-old women) of malignant mixed müllerian tumor (MMMT) following radiation therapy for uterine cervical cancer sixteen and twenty years ago respectively were reported. They were admitted due to abdominal pain and diagnosed as ileus. In the first case, CT examination revealed a tumor measuring about 8 x 10 cm in size in the uterine posterior wall. Recurrence of the uterine cancer was suspected and hysterooophorectomy combined with sigmoidectomy was performed. In the second case, artificial anus formation was performed because of sigmoid stricture by the invasion of the tumor. Histologically, tumors in both cases were composed of carcinomatous and sarcomatous components including heterologous elements such as cartilage. The patients died of extensive spreads and metastasis in the liver and alimentary tract.

Aged↗
PubMed1995

[Detection of mutation in insulin receptor gene in patients with essential hypertension].

We have analyzed single-stranded conformational polymorphism (SSCP) to screen for mutation in exon 17 of insulin receptor gene in 46 patients with hypertension and 49 normotensive controls. Three different SSCP patterns were detected in both patients and controls and the frequency of pattern I was 54.3% and 32.7% (chi 2 = 3.71, P = 0.05) in patients and controls respectively; The frequency of pattern II was 61.3% and 26.1% (chi 2 = 10.49, P = 0.001) in controls and patients respectively; the frequency of pattern III did not differ between controls and patients. Based on direct sequencing, the differences between pattern II and pattern I were explained by a mutation substituting at position 1040, GAG1040-->GAA1040, which suggests that codon GAA1040 may be a genetic marker for susceptibility to essential hypertension in Chinese.

Adult↗
PubMed1994

Molecular cloning of a proteolytic antibody light chain.

The cDNA for an antibody light chain raised by immunization against vasoactive intestinal peptide (VIP) was cloned in a bacterial expression vector, and the recombinant light chain was purified to electrophoretic homogeneity. The light chain catalyzed the hydrolysis of VIP efficiently owing to its comparatively high affinity for the substrate. In control experiments, the catalytic activity was preserved at a constant level after further chromatography of the light chain on anion-exchange and gel-filtration fast protein liquid chromatography columns, and it was removed by immunoadsorption with immobilized anti-mouse light chain antibody. The amide bond linking methylcoumarinamide (MCA) and arginine in a tripeptide unrelated in sequence to VIP was cleaved by the light chain with lower affinity and kinetic efficiency (kcat/Km). Hydrolysis of the peptidyl-MCA conjugate was inhibited competitively by the alternate substrate, VIP. The Ki and Km values for VIP were in the same range, indicating that peptide-MCA and VIP hydrolysis occurs at a common catalytic site in the light chain. Molecular modeling suggested the presence of a serine protease-like site in the light chain. This was supported by inhibition of the hydrolytic activity by serine protease inhibitors, but not by inhibitors of other classes of proteases. These observations suggest a poorly discriminatory catalytic site, with specificity for VIP arising chiefly by means of the antigen recognition function of the light chain combining site.

Amino Acid Sequence↗
PubMed1994

Modification of a whole room indirect calorimeter for measurement of rapid changes in energy expenditure.

Whole room indirect calorimeters are among the most accurate devices for measurement of human energy expenditure and have provided useful data about determinants of total daily energy expenditure. However, a limitation of whole room indirect calorimeters has been the inability to detect acute (usually < 10-15 min) changes in energy expenditure. This precludes using these devices to study the acute effects of food, drugs, or exercise on energy expenditure. We describe modifications made to our whole room indirect calorimeter (respiratory chamber) to allow accurate measurement of energy expenditure over time periods as short as 1 min. The modifications involve changes in the system design and use of signal processing techniques. With these modifications, we can measure energy expenditure in 1-min intervals throughout the day. This allows accurate study of the acute effects of food, exercise, or drugs on energy expenditure in subjects moving freely inside the respiratory chamber. The ability to use respiratory chambers for these types of studies should improve our understanding of how body weight is regulated.

Calorimetry↗
PubMed1994

Cardiorespiratory behavior during sleep in full-term and preterm neonates at comparable postconceptional term ages.

Cardiorespiratory behavior during sleep has been investigated by comparing visually analyzed minutes of EEG sleep with the digitized values of these two physiologic variables for each corresponding minute. Continuous 3-h nighttime sleep studies on 37 full-term and preterm neonates at comparable postconceptional term ages were acquired under controlled conditions, using a 24-channel computerized monitoring system and an automated event-marker program. Five thousand, two hundred ninety-four minutes were assigned an EEG state by traditional criteria. Eighteen preterm infants were compared with 19 full-term infants with respect to six cardiac and six respiratory measures: two nonspectral calculations (i.e. average per minute and variance of the means) and four spectral calculations of the cardiorespiratory signal (i.e. bandwidth, spectral edge, mean frequency, and ratio of harmonics). The relative capabilities of these measures to predict a sleep state change were investigated using discriminant analysis. A stepwise selection algorithm in discriminant analysis was used to identify the order of significance for the remaining variables. Eight cardiorespiratory measures were then submitted to multivariate analysis of variance to assess sleep state or preterm-full-term differences: mean frequency, bandwidth, average per minute, and ratio of harmonics for cardiac signals; and spectral edge, mean frequency, logarithm of variance, and ratio of harmonics for respiratory signals. Differences among the sleep states and between neonatal groups were highly significant (p < 0.0001). Interaction between sleep state and neonatal group was also significant (p < 0.034). Two variables differentiated preterm from full-term respiratory behavior: ratio (p < or = 0.001) and mean frequency (p < or = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular Physiological Phenomena↗
PubMed1994

Screening anti-HIV Chinese materia medica with HIV and equine infectious anemic virus reverse transcriptase.

The inhibitory activities of human immunodeficiency virus reverse transcriptase (HIV-RT) inhibitors PFA and Suramin against HIV-RT and equine infectious anemic virus reverse transcriptase (EIAV-RT) were studied in this paper. The 50% inhibitory concentration (IC50) of HIV-RT and EIAV-RT treated by PFA and Suramin were 0.2 mumol, 9.8 mumol and 17 mumol, 19.9 mumol, respectively. More than thirty Chinese medicines, including recipes, herbs, extracts of traditional materia medica and isolated compounds were tested using HIV-RT and EIAV-RT as target enzymes. It was found that 5 crude extracts such as Rhizoma Polygoni Cuspidati, and Radix Notoginseng, 7 isolated compounds like Flavone of Ramulus Visci, Flavone of Ajuga Decumbens Thumb, and Aristolochic acid, as well as the extract of the complex prescription Xiao Chai Hu Tang have shown various inhibitory actions on these two enzymes. The activities of the two enzymes were comparable, but HIV-RT was more sensitive, suggesting that HIV-RT can be used as index for the screening of anti-aids drugs.

Animals↗
PubMed1993

Effect of immune RNA on NK activity of infants born to mothers with cytomegalovirus infection.

The effect of specific immune RNA (i-RNA) on the activity of natural killer (NK) cells in the peripheral blood of 27 newborn infants was studied by lactic dehydrogenase (LDH) release assay. Peripheral blood mononuclear cells (PBMC) were used as effector cells with K-562 tumour cells as target cells. The results showed that in the therapeutic group (n = 17) the average activity of NK cells after therapy (24.13 +/- 4.62%) was 13.67 +/- 5.79% higher than before therapy (10.47 +/- 3.57%). In the control group (n = 10) these were only 10.78 +/- 3.94% and 11.58 +/- 3.37%, the difference was not statistically significant (P > 0.05). However, NK activity in the therapeutic group and control group was markedly different (P < 0.01). The data indicate that specific i-RNA can enhance the activity of NK cells in the peripheral blood of newborn infants. Therefore, we believe that specific i-RNA may play an important role in defence against CMV infection. The mechanism of i-RNA augmenting NK cellular activity is also discussed.

Cytomegalovirus↗
PubMed1992

Peptidolytic monoclonal antibody elicited by a neuropeptide.

We report evidence that a monoclonal antibody raised by immunization with a vasoactive intestinal peptide (VIP)-carrier protein conjugate selectively hydrolyzes VIP and a fluorescence quenched decapeptide (FQ14-22D), representing the region of VIP most susceptible to autoantibody-mediated cleavage (residues 14-22). A high affinity of the antibody for VIP and a lower affinity for FQ14-22D were revealed by kinetic studies and further substantiated by potent inhibition of FQ14-22D cleaving activity by full-length VIP. Sequencing of FQ14-22D hydrolysis products indicated selective cleavage at one peptide bond. These observations suggest that antibodies induced against naturally occurring polypeptide antigens can express peptidolytic activity targeted for specific sequences in the recognition epitope.

Amino Acid Sequence↗