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Biomedical subjects

W I Lee

Publications and source records attributed to W I Lee.

At least 19 recordsLinked to original sources

Pharmacokinetics and antitumour activity of a new anthracycline, DA-125, after intravenous administration to subcutaneously implanted Lewis-lung-carcinoma-bearing mice.

The pharmacokinetics and tissue distribution of M1-M4 were compared after intravenous (i.v.) administration of DA-125, 25 mg kg-1, to BDF1 mice (n = 5 at each sampling time) and subcutaneously implanted Lewis-lung-carcinoma-bearing BDF1 mice (n = 10 at each sampling time. The mean plasma concentrations of M1-M4 were not significantly different between the two groups of mice, and hence similar pharmacokinetic parameters for M1-M4 were obtained. The amount of M1 in the lung was significantly greater in the tumour-bearing mice than in the control mice, resulting in a greater AUAt in the tumour-bearing mice (18,600 against 8940 micrograms min g-1), and vice versa in the liver (962 against 3840 micrograms min g-1). However, the corresponding values for other tissues were comparable between the control and tumour-bearing mice. The amount of M1 was greatest in the lung for up to 2 h in the tumour-bearing mice. M2 was the predominant metabolite among M1-M4 excreted in 24 h urine by both groups of mice; 8.36 and 10.7% of the i.v. dose were excreted in 24 h urine as M2--expressed in terms of DA-125--by the control and tumour-bearing mice, respectively. The amount of M1 in the tumour mass reached a mean Cmax of 3.75 micrograms g-1 immediately after i.v. administration of DA-125 to the tumour-bearing mice, then declined very slowly to an amount that remained almost constant for up to 24 h. This suggested that M1 has high affinity for the subcutaneously implanted Lewis lung carcinoma. The antitumour activity, such as the increase in life span (ILS) and tumour growth inhibition (TGI) of DA-125, 6-48 mg kg-1, and adriamycin (ADM), 3-18 mg kg-1, were also compared in subcutaneously implanted Lewis-lung-carcinoma-bearing BDF1 mice after four weekly i.v. administration of the drugs on days 1,8,15, and 22 following tumour implantation. More than three out of six mice survived as tumour-free for longer than 70 d at a DA-125 dose range of 6-24 mg kg-1, but there were no tumour-free mice at any dose of ADM. Assuming ILS values higher than 30% to be effective, DA-125 doses ranging from 6 to 24 mg kg-1 were effective in increasing the life span, which ADM does only within the dose range of 6-12 mg kg-1.

Animals

Bone marrow findings before and after treatment with recombinant human erythropoietin in chronic hemodialyzed patients.

The stimulating effect of rHuEPO on erythropoiesis has been shown in several studies, using bone marrow cell culture or animal models. To investigate the effect of rHuEPO on bone marrow findings in vivo, we studied the bone marrow cellularity, the myeloid: erythroid (M:E) ratio, an estimate of the number of megakaryocytes, any cytomorphologic or maturation abnormalities, and an estimate of the storage iron before and after 3 months of treatment with rHuEPO in 10 chronic hemodialyzed patients. Nine patients showed a slight or moderate decrease of erythropoiesis in bone marrow in comparison to normal bone marrow before rHuEPO treatment. The bone marrow cellularity was a mean of 28.5% and decreased in 8 out of 10 patients compared to normal values. However, megakaryopoiesis and granulopoiesis were normal. Three months of treatment with rHuEPO had increased erythropoiesis in all 10 patients, including one patient whose bone marrow proved to be normal erythropoiesis on baseline examination. The M:E ratio was significantly decreased from 4.0 +/- 1.2:1 to 2.4 +/- 1.1:1 (p < 0.005). The bone marrow cellularity was also increased in 9 patients, except in 1 patient whose specimen was inadequate for diagnosis, after 3 months of treatment with rHuEPO. On baseline examination of bone marrow, iron staining was undetectable in one, low in one, normal in 2 and high in 5 sections. According to grading, iron staining had decreased from 3.1 +/- 1.7 to 2.1 +/- 0.9 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Bone marrow involvement by non-Hodgkin's lymphom.

We retrospectively studied 156 patients with non-Hodgkin's; ymphoma (NHL) in order to evaluate the incidence of bone marrow (BM) involvement at the time of diagnosis. The incidence of marrow involvement in NHL was 35% (55 patients). The most common histologic type of lymphoma was diffuse large cell lymphoma with 30% of the cases having bone marrow involvement. The highest incidence of marrow involvement was seen in immunoblastic lymphoma & the lowest incidence in diffuse mixed cell lymphoma. Bone marrow lymphoma was present in 50% of low-, 34% of intermediate-, and 55% of high-grade lymphomas. B-cell vs T-cell lymphoma in cases of marrow involvement was 56% to 42%. The most frequent pattern of marrow involvement was interstitial & diffuse (56% & 31%). The paratrabecular pattern was rare (4%). Most lymphomas (42%) extensively involved marrow space greater than 76% of the total marrow space. Discordant histology between lymph node and BM was seen in 10 cases (18%). Biopsy was the best method compared to smear & clot section (sensitivity 82% vs 72% vs 69%). In conclusion, our study revealed that the most common histologic type of marrow lymphoma was diffuse large cell type with frequent interstitial and diffuse pattern and extensive involvement of the marrow space. No predilection for a trabecular pattern was found. This result was in contrast to that in the Western literature.

Adolescent

Pelvic actinomycosis with colo-ileo-vesical fistula formation: report of a case.

Pelvic actinomycosis with multiple fistular formation is rarely reported in the literature. We herein present a case of pelvic actinomycosis with sigmoid colo-ileovesical fistulae in a 36-year-old intrauterine device (IUD) user. She was admitted to the hospital because of general malaise, weight loss and bilateral palpable adnexal masses. Sonography showed bilateral adnexal masses which contained many echolucent spots. A barium enema examination revealed sigmoid colo-ileo-vesical fistulae. A computed tomographic scan showed bilateral cystic adnexal masses, bilateral hydronephrosis and hydroureter. Preoperatively, pelvic malignancy was suspected. An exploratory laparotomy was performed. Bilateral tubo-ovarian abscesses with extensive adhesions were found. Pathologic examination of the operative specimen revealed pelvic actinomycosis. The patient was treated with penicillin for 14 weeks and had a stable clinical course.

Actinomycosis

Selection of human spermatozoa according to their relative motility and their interaction with zona-free hamster eggs.

Human spermatozoa were separated according to their motility by centrifuging semen on discontinuous Percoll gradients. Fractions of the gradients were examined for sperm motility, velocity, viability, morphology, bacteria, and sperm function using the hamster ova sperm penetration assay. The percentage of motile sperm increased from 40% to 60% motile sperm in 60% Percoll to 90% to 100% Percoll. Sperm velocity increased proportionately. Staining showed that greater than 90% of sperm in the 100% Percoll were alive and had normal morphology, and that only sperm cells were found in Percoll concentrations greater than 80%. Sperm isolated in the 80% to 100% Percoll fractions penetrated hamster ova much more frequently than sperm found in the 60% to 70% fractions or than sperm that had not been separated on a Percoll gradient.

Cell Separation

Laser light-scattering study of the effect of washing on sperm motility.

The effect of washing on human sperm motility was measured by means of dynamic laser light-scattering spectroscopy. Semen samples from 24 fertile donors were diluted with Biggers, Whitten and Whittingham (BWW) medium and subsequently centrifuged at one of the following forces: 235 x g, 325 x g, 400 x g, 470 x g, 500 x g, 600 x g, and 800 x g. The duration of centrifugation was 8 minutes for the first wash, 6 minutes for the second wash, and 3 minutes for the third wash. Sperm motility was evaluated in terms of the root mean square swimming speed of the spermatozoa and the mean migration rate of washed spermatozoa in estrous bovine cervical mucus (BCM). It was found that sperm motility and viability were improved when semen samples were washed at 235 x g, even after three washes. However, washing at forces of 600 x g or more reduced sperm motility and also their ability to penetrate cervical mucus in vitro. Repeated washing at forces between 300 x g and 500 x g had little deleterious effect on sperm motility.

Cell Separation

Sperm penetration into cervical mucus in vitro. III. Effect of freezing on estrous bovine cervical mucus.

The influence of the storages period on estrous bovine cervical mucus after it was stored in the freezing compartment of the laboratory refrigerator was evaluated by an in vitro sperm penetration test with human spermatozoa, laser light-scattering, and a spinnbarkeit test. Data obtained from the sperm penetration test were analyzed by a mathematical model that correlates the sperm motility with the sperm transport rate and the penetrability of the mucus. The tests showed that estrous bovine cervical mucus can be stored for up to 4 weeks at -12 degrees C without a change in its physical properties. The results of this study strengthen the suggestion that bovine mucus could be employed as a substitute for human cervical mucus.

Animals

A stochastic model for oviductal egg transport.

A mathematical description of ovum transport based on Langevin's diffusion equation is presented. The proposed model is deduced from qualitative features of this phenomenon, not induced from numerical fitting of experimental data. We demonstrate that egg transport in the ampulla of the rabbit oviduct can be represented as a one-dimensional random walk in a field of external force. The application of the model to describe isthmic ovum and sperm transport on the basis of simple random walk process is also discussed. The present formulation identifies and characterizes the forces involved in the motions of the ovum and predicts specific alternatives for physiological regulation of egg transport in the oviduct.

Animals

Sperm penetration into cervical mucus in vitro. II. Human spermatozoa in bovine mucus.

Human spermatozoa pentrate estrous bovine cervical mucus readily in vitro and maintain good motility and viability for a number of hours. They show pronounced unidirectional motion in mucus that has been aligned linearly. Data from tube preparations indicate that human spermatozoa from a given ejaculate travel more rapidly in estrous bovine mucus than in human midcyle mucus. They are prevented from penetrating luteal phase bovine mucus. The results are discussed in relation to a model of the molecular structure of cervical mucus, derived from laser light-scattering spectroscopy. In addition, it is suggested that bovine cervical mucus could be developed as a possible substitute for human cervical mucus in cases of infertility due to deficient endogenous mucus.

Animals

Sperm penetration into cervical mucus in vitro. I. Comparative studies.

Comparative studies have been carried out on the behavior of human and bovine spermatozoa toward homologous cervical mucus in vitro. In both cases the degree of sperm penetration and the pattern of sperm motility were influenced in a characteristic fashion by prior manipulation of the mucus: the most rapid and extensive penetration, and pronounced unidirectional motion, were seen in mucus that had been aligned linearly. By contrast, spermatozoa from rabbits, guinea pigs, rats, and mice were largely prevented from entering either midcycle human or estrous bovine cervical mucus, regardless of its physical arrangement. The observations on sperm motility patterns and the degree of penetration are discussed in relation to a model of the molecular arrangement of cervical mucus, derived in our laboratory from laser light-scattering spectroscopy.

Animals

Laser light-scattering study of the effect of progesterone on sperm motility.

It is known that progestins can induce in the secretory cells of the cervix the excretion of a mucus that is highly viscuos, scanty, and impenetrable to spermatozoa. Mucus of this type is similar to that excreted during the luteal phase of the normal human menstrual cycle and the cow estrous cycle. It is a natural sequence to ask the question, do progestins also have a direct effect on sperm motility? With dynamic laser light-scattering we measured the motility of freshly washed human spermatozoa and of spermatozoa in the presence of a progesterone, both in terms of their swimming speed distribution as expressed in the spectrum of scattered light. The swimming speed was significantly reduced when the concentration of progesterone was three orders of magnitude greater than that of the physiologic level. This finding confirms the finding in earlier biochemical studies that progesterone has a distinct spermiostatic effect. We suggest this answer to the above question: progestin-releasing contraceptive devices may act on spermatozoa directly as well as in the secretory cells of the cervix.

Animals

Molecular arrangement of cervical mucus: a reevaluation based on laser light-scattering spectroscopy.

Evidence obtained from laser light-scattering spectroscopy suggests that the molecular arrangement of cow estrous cervical mucus is an ensemble of entangled random-coiled macromolecules rather than a cross-linked macromolecular network, the model heretofore widely accepted. This new model can account for the following phenomena: (1) The viscoelastic properties of the estrous mucus and human mid-cycle cervical mucus are the result of the way in which the glycoproteins are entangled. Variations of these properties during the reproductive cycle may simply be due to changes in the water content of the cervical mucus. (2) Penetration of spermatozoa in mucus may be entirely mechanical without involving any kind of enzymatic lysis of cross-links (this is supported by changes in the pattern of spermatozoa flagellation during sperm penetration of cervical mucus as shown in motion picture films). (3) The orientation of spermatozoa in the cervical muscus need not be due to the presence of 'channels' between micelles but simply to an artifact, the stretching or flow of the mucus, which orients the entangled macromolecules and thus facilitates the penetration of spermatozoa in an axis parallel to them.

Animals

Laser light-scattering spectroscopy: a new application in the study of ciliary activity.

A uniquely precise and simple method to study ciliary activity by laser light-scattering spectroscopy has been developed and validated. A concurrent study of the effect of Ca2+ on ciliary activity in vitro by laser scattering spectroscopy and high speed cinematography has demonstrated that this new method is simpler and as accurate and reproducible as the high speed film technique.

Cilia