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Biomedical subjects

M Hu

Publications and source records attributed to M Hu.

At least 217 records · Page 12Linked to original sources

Membrane permeability parameters for some amino acids and beta-lactam antibiotics: application of the boundary layer approach.

The boundary layer approach to analyzing the results of the perfused intestinal segment method of measuring membrane permeabilities is applied to the amino acids; leucine, valine, phenylalanine, lysine and aspartic acid and the beta-lactam antibiotics, cephalexin and penicillin V. The analysis indicates that in determining the membrane parameters, Pw vs. Cw data are preferable to using Jss = PwCw vs. Cw data. It is further shown that the carrier permeability, Pc* = Jmax*/Km, may be the most significant parameter to consider since luminal amino acid or drug concentration may generally be below the Km value. A comparison of P*c values for the beta-lactams with results for passively absorbed compounds indicates that the cephalosporins would be expected to be well absorbed orally based on the perfusion results. This suggests that this approach may be useful in estimating oral drug absorption for compounds that are absorbed passively as well as by a carrier-mediated mechanism.

Amino Acids↗

Passive and carrier-mediated intestinal absorption components of captopril.

The intestinal absorption mechanism of captopril was investigated in fasted rats using a single-pass perfusion method. Captopril and captopril disulfide were analyzed by HPLC. A modified boundary-layer solution was applied to determine the apparent intestinal wall permeabilities (Pw*). The results indicated that captopril is very permeable in the small intestine but not in the colon, and the permeability in the small intestine is both pH and concentration dependent. The estimated parameters for the carrier are: Km*, 6 mM; Jmax*, 12 mM; and Pc*, 2. There is also a significant passive component to captopril absorption in the small intestine. Furthermore, the intestinal permeability of captopril was significantly decreased by the withdrawal of sodium from the perfusate (3 times), and the addition of 85 mM of gly-gly (2.5 times), 15 mM of gly-pro (4 times), dipeptide mixture (4.5 times), 0.5 mM of 2,4-dinitrophenol (4 times), and 10 mM of cephradine (6 times). This is the first demonstration that an angiotensin converting enzyme (ACE) inhibitor is at least in part transported by a carrier-mediated process in the intestine via the peptide carrier system. In addition, the results showed that the peptide carrier system can transport a substrate without a "N" terminal nitrogen atom.

Animals↗

[Kinetic observation and analysis of the radioactivity distribution of 125I-labelled F(ab')2 fragments of monoclonal antibody against human lung cancer cells in normal mice].

Radioactivity distribution of 125I-labelled F(ab')2 fragments in 14 organs and tissues of normal mice for 11 time-phases from 0.5 hour to 7 days after injection was observed. The radioactivity-time curves of these organs and tissues were divided into three types according to their characteristics: excreting type (blood and liver), absorbing type (thyroid), absorbing-excreting type (the other organs and tissues). The organs fully perfused with blood had shorter peak-time and higher peak-value, such as heart, lung, kidney and liver. All of the peak-times were equal to or less than 2 days after injection, therefore the image taking should be kept away from this period. The excreting rate constants of slow metabolic component were similar for various organs and tissues except thyroid and brain. The brain had a low peak in the curve and small excreting rate constant. It was demonstrated that F(ab')2 fragments were able to penetrate the blood-brain barrier but absorption and excretion were slower compared with the other organs and tissues. The radioiodine was obviously concentrated in the subcutaneous tissue, which may have been the main cause of the subcutaneous tissue tumor induced by radioiodine. The radioactivity-time curve in which the peak value and inflect point existed simultaneously shows that radioactivity metabolism after injection of 125I-F(ab')2 follows three compartment models. The biological meanings corresponding to three sections of the blood radioactivity-time curve are pure distribution, distribution-recycle and catabolic-excretory phases, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Quantitative homogeneous enzyme immunoassays for amitriptyline, nortriptyline, imipramine, and desipramine.

We describe specific EMIT homogeneous enzyme immunoassays for amitriptyline, nortriptyline, imipramine, and desipramine in patients' serum samples. Before analysis, an easily performed extraction step involving the use of 500 microL of sample and a 1-mL disposable column eliminates cross-reacting polar metabolites. The range of the standard curve for the first three drugs is 25 to 250 micrograms/L, and for desipramine is 50 to 500 micrograms/L. Within-run and between-run CVs are less than 10% throughout the range of the assays. Results for patients' samples obtained by this method and by "high-performance" liquid chromatography compare well, showing a slope range of 0.94-1.04 and correlation coefficients ranging from 0.93 to 0.96, depending on the assay.

Amitriptyline↗

Randomized double-blind comparison of nifedipine and isosorbide dinitrate therapy in variant angina pectoris due to coronary artery spasm.

Twelve patients were entered prospectively into a randomized double-blind study comparing the efficacy of nifedipine and isosorbide dinitrate (ISDN) in the treatment of variant angina pectoris due to coronary artery spasm. Using the diary technique, both anginal episodes and nitroglycerin tablets consumed were recorded during the pretrial, no drug period, and both active drug phases. During the baseline pretrial period, an average of 1.1 anginal episodes/day occurred with reduction to 0.28/day during nifedipine treatment and 0.39/day during ISDN treatment. Headache was the major side effect during ISDN treatment, occurring in 9 of 11 (81%) patients; and nonheart failure related pedal edema during nifedipine treatment, occurring in 4 of 12 (33%) patients. Intolerable side effects necessitating cessation of treatment occurred in two patients during nifedipine treatment and in three patients during ISDN treatment. Patients preferred nifedipine over ISDN because of increased efficacy and fewer uncomfortable side effects. We conclude that both nifedipine and ISDN are effective therapy for coronary spasm, but that nifedipine was more effective and was preferred by the majority of patients.

Adult↗

Mapping of IS1 elements flanking the argF gene region on the Escherichia coli K-12 chromosome.

Two directly-repeated IS1 elements have been mapped on the Escherichia coli K-12 chromosome at positions 23.2 kb and 34.5 kb counterclockwise of the IS3 element alpha3beta3 by using F-prime plasmids (including the F lac- proAB+ plasmid F128) that carry different portions of the bacterial chromosome in the purE to proA region. Mapping was accomplished in part by construction of EcoRI, BamHI, and BglII restriction enzyme cleavage maps. Electron microscope heteroduplex and hybridization studies indicate that the chromosomal region flanked by these IS1 elements is completely homologous to the IS1-argF-IS1 region (Tn2901) on the P1argF5 transducing phage (York and Stodolsky, 1981), which suggests that the argF gene region in the usual E. coli K-12 strains has a transposon-like structure.

Chromosome Mapping↗

Comparison of IS1, IS2 and IS3 copy number in Escherichia coli strains K-12, B and C.

The number of copies of IS2 and IS1 in the chromosomes of five Escherichia coli K-12 strains and E. coli B and E. coli C has been determined by hybridization. Among these strains, IS1 copy numbers range from 4 to 19 and IS2 copy numbers range from 0 to 12. IS2 is present once in the E. coli B chromosome, but it is absent from E. coli C. The copy numbers of IS3 in the same seven E. coli strains range from 4 to 6.

Bacteriophage lambda↗

Do patients in whom myocardial infarction has been ruled out have a better prognosis after hospitalization than those surviving infarction?

To determine the prognosis after hospitalization of patients hospitalized with acute chest pain in a coronary-care unit, we undertook a prospective study of 211 consecutive admissions to the Stanford Coronary Care Unit. On the basis of predetermined criteria, 16 patients were found to have noncardiac chest pain, and myocardial infarction was ruled out in 89, one of whom died in the hospital. Infarction was documented in 84 others, six of whom died in the hospital. Prospective follow-up after hospitalization was carried out in the 88 patients in whom infarction was ruled out and in the 78 patients who survived infarction. The rate of myocardial infarction or death was 8.0 per cent at six months and 21.6 per cent at a mean of 27.8 months of follow-up for patients who had infarction ruled out, as compared with 7.7 per cent at six months and 21.8 per cent at a mean of 27.8 months of follow-up for those who had a documented infarction during the initial hospitalization. Cardiomegaly, congestive heart failure, and angina after discharge from the hospital tended to increase the risk of morbidity and mortality in both groups. The patient hospitalized with acute ischemic chest pain without evolution of a myocardial infarction has a six to 24-month prognosis similar to that of the patient hospitalized with an acute infarction, and therefore requires similar diagnostic and therapeutic assessment.

Angina Pectoris↗

Prodromal characteristics as indicators of cardiac events in patients hospitalized for chest pain.

In an effort to determine the usefulness of prodromata for predicting a myocardial infarction, a prospective analysis was made of 211 consecutive patients with chest pain who were admitted to the Stanford University Medical Center Coronary Care Unit. In their subsequent course, 91 patients had a myocardial infarction, 102 had a myocardial infarction ruled-out, and 18 had a noncardiac etiology for their chest pain. Prodromal chest pain in the previous six months had occurred in 65% of patients and unstable angina in 61%. Infarction versus noninfarction patient groups could not be identified on the basis of prodromal ill health, chest pain, unstable angina, typical versus atypical nature of the chest pain, or activity at the onset of pain. Complaints of preceding fatigue and increased perceived stress were common in both groups. Activity at the onset of the admission chest pain was strenuous in 15% of the infarction patients and 12% of the noninfarction patients. We conclude that prodromal symptoms are common in both infarction and noninfarction patients. Although chest pain probably remains the single most frequent identifier of a new cardiac event, it is common in noninfarction patients and cannot be used alone to predict infarction or death.

Adult↗

Enumeration and identification of IS3 elements in Escherichia coli strains.

Escherichia coli K-12 strains ordinarily contain five IS3 elements. Three of these correspond to previously mapped IS3 elements (R. C. Deonier, G. R. Oh, and M. Hu, J. Bacteriol. 129:1129--1140, 1977; S. Hu, E. Ohtsubo, and N. Davidson, J. Bacteriol. 122:749--763, 1975), and two additional IS3 elements are identified. The distribution of IS3 elements among deoxyribonucleic acid fragments generated by digestion with EcoRI indicates a basic pattern from which deviation is detected.

Base Sequence↗

Coronary bypass surgery for unstable angina pectoris. Long-term survival and function.

The first 81 patients to undergo coronary artery bypass surgery for unstable angina pectoris at Standford Hospital have been observed for a mean of 40.8 months. Surgical mortality was 8.5%, and perioperative incidence of myocardial infection was 16%. The mean 18-month follow-up showed two early cardiac deaths and 12 additional myocardial infarctions. Sixty-seven percent of the patients were angina-free, and the condition of none was worse. After a mean of 40.8 months, two late cardiac deaths and two myocardial infarctions had occurred. Complete relief of angina was present in 51%;22% had unstable or worsening angina. The probability of survival from time of operation to four months after surgery was 88.8% +/- 3.5%, and this remained unchanged until the two late deaths, which decreased survival probability to 83.8% +/- 4.8% at 43 months. The two late cardiac deaths and the 22% incidence of patients with worsening angina may reflect progression of the atherosclerotic process, late graft occlusion, or both.

Adult↗

Further mapping of IS2 and IS3 in the lac-purE region of the Escherichia coli K-12 genome: structure of the F-prime ORF203.

The sequence organization of the F-prime ORF203 was determined by heteroduplex analysis. This large, type II F-prime (Scaife, 1967) contains lac, proC, and purE genes derived from the W1485 subline of Escherichia coli K-12. The IS3 and IS2 elements previously found in the lac-proC-purE region derived from the 58-161 subline (Hu et al., 1975) are also present in the same locations in the bacterial deoxyribonucleic acid (DNA) from the W1485 subline. Recombination between the IS2 region of F and an IS2 element located between lac and proC on the bacterial DNA apparently led to the formation of the perental Hfr, OR21. IS2 is thus directly repeated, with one copy of each element appearing at each of the two junctions between F and the bacterial sequences on ORF203. The F plasmid is found together with ORF203 in the plasmid DNA, and this probably forms from ORF203 by recombination between the directly repeated IS2 elements. ORF203 appears to have been excised from the Hfr chromosome by recombination between the IS3 sequence alpha3beta3 located counterclockwise of lac and the directly repeated IS3 sequence alpha4beta4 located clockwise of purE.

Chromosome Mapping↗

Protein value of two imitation milks. Chemical and biologic assays.

Two imitation powdered milk products were compared with whole milk for both quantity and quality of protein. One product had comparable quantity of protein, but inferior quality, while the other had comparable quality but inferior quantity. Therefore, neither was equivalent to whole milk when a reconstituted serving of the product was calculated in terms of the U.S. RDA. However, a single serving of either product would constitute 10 per cent of the U.S. RDA for protein. Calcium contribution in terms of U.S. RDA would also be significant, but would not equal whole milk for these particular products. Thus ingredient composition varies widely for imitation milk products. These products were not evaluated for other nutrients, such as fats and vitamins.

Adult↗