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Biomedical subjects

M K Park

Publications and source records attributed to M K Park.

At least 19 recordsLinked to original sources

Suppression of the development of uterine adenomyosis by danazol treatment in mice.

Inhibitory effects of danazol, an isoxazol derivative of synthetic steroid 17 alpha-ethinyl-testosterone, on the development of uterine adenomyosis, a pathological disorder of endometrial tissue defined as the presence of endometrial glands and stroma in the myometrium, were investigated in mice of SHN strain. Mice treated with 0.5 microgram danazol for 5 weeks during 4-9 weeks of age and killed at 21 weeks of age showed significantly lower incidence of the spontaneous development of adenomyosis than the age-matched intact control mice. The inhibitory effects of danazol were also evident in mice bearing pituitary isografts which were effective in inducing an early and a high incidence of adenomyosis. Furthermore, the treatment with danazol resulted in the decrease of serum levels of luteinizing hormone (LH) and prolactin (PRL) associated with hypofunction of ovaries and persistent diestrus. These results support the usefulness of danazol for the clinical treatment of gynecological disorders except for hypofunction of ovaries.

Animals

Oxygen tensions and infections: modulation of microbial growth, activity of antimicrobial agents, and immunologic responses.

Oxygen tensions play an important role in the outcome of infections. Oxygen is cidal or static for microorganisms that lack defenses against oxidants. Hyperoxia and hyperbaric oxygen exert antimicrobial effects by increasing the intracellular flux of reactive oxygen species. In bacteria, such species cause DNA strand breaks, degradation of RNA, inhibition of amino acid biosynthesis, and inactivation of membrane transport proteins. Oxygen tensions also affect the activity of antimicrobial agents. In general, hyperoxia potentiates while anaerobiosis decreases the activity of many antimicrobial drugs. With regard to host defenses, hyperoxia elevates oxygen tensions in infected tissues to levels that facilitate oxygen-dependent killing by leukocytes. Prolonged hyperoxia inhibits DNA synthesis in lymphocytes and impairs chemotactic activity, adherence, phagocytic capacity, and generation of the oxidative burst in polymorphonuclear leukocytes and macrophages.

Animals

Hormonal modulation of prolyl endopeptidase and dipeptidyl peptidase IV activities in the mouse uterus and ovary.

Prolyl endopeptidase and dipeptidyl peptidase IV are proline-specific peptidases, and are ubiquitously distributed in various tissues in mammals. The specific activities of these peptidases in both uterus and ovary were examined in the SHN strain of mice at estrus or diestrus. A marked change in prolyl endopeptidase activity was found in the uterus and ovary in intact mice during the estrous cycle, the activity being high at estrus and low at diestrus. In ovariectomized mice, prolyl endopeptidase activity was significantly higher in the uterus treated with progesterone or estradiol than in the uterus treated with vehicle oil only or a dopamine antagonist (perphenazine) which stimulates prolactin secretion. On the other hand, notable change in dipeptidyl peptidase IV activity during the estrous cycle was found only in the uterus of intact mice. The activity was low at estrus and high at diestrus. In ovariectomized mice, the uterus exposed to estradiol showed a lower dipeptidyl peptidase IV activity than the uteri treated with progesterone, the dopamine antagonist or vehicle oil. These findings reveal that there is a close correlation between the circulating level of ovarian steroids and the activities of these proline-specific enzymes.

Animals

Antibodies against the SV40 large T antigen nuclear localization sequence.

Transport of large proteins into the nucleus requires both a nuclear localization signal (NLS) and exposure of that signal to components of the transport machinery. In this report, polyclonal and monoclonal antibodies were generated against the NLS of SV40 large T antigen. Several of these antibodies immunoprecipitated large T antigen produced by in vitro transcription-translation and recognized T antigen expressed in cultured cells. Binding of the antibodies to T antigen was quantified using an indirect radioimmunoassay and found to be specifically inhibited by peptides corresponding to the T antigen NLS. The ability of NLS-specific antibodies to recognize large T antigen suggests that the NLS is exposed on the surface of T antigen. When one of the NLS-specific monoclonal antibodies was introduced into the cytoplasm of cells expressing T antigen, the antibody remained cytoplasmic. These results suggested either that cytoplasmic components compete for binding to the NLS or that the antibody dissociates from T antigen during transport into the nucleus. When an antibody directed against an epitope distinct from the NLS was microinjected into the cytoplasm of cells expressing large T antigen, both the antibody and antigen were transported into the nucleus. The observed stability of the antigen-antibody complex strongly suggest protein unfolding is not required for nuclear protein transport.

Amino Acid Sequence

Differential appearance of the subunits of glycoprotein hormones (LH, FSH, and TSH) in the pituitary of bullfrog (Rana catesbeiana) larvae during metamorphosis.

The ontogeny of gonadotrophs and thyrotrophs in the bullfrog pituitary was examined immunohistochemically using monoclonal antibodies against bullfrog lutropin beta-subunit (LH beta), follitropin beta-subunit (FSH beta) and its alpha-subunit, and polyclonal anti-human thyrotropin beta-subunit (TSH beta) serum. Immunoreactive alpha-subunit- and TSH beta-, but not FSH beta- and LH beta-containing cells were observed at embryonic stage 24 (Shumway's classification). Immunoreactive FSH beta cells first appeared at Taylor-Korllos stage V, and immunoreactive LH beta cells at stage X. Throughout metamorphosis, several gonadotrophs containing both FSH and LH were found in the ventrocaudal region, but most gonadotrophs contained only FSH. Immunoreactive alpha-subunit cells were always more frequent than the sum of immunoreactive beta-subunit cells, which was confirmed by quantitative studies using immunohistochemical and RIA techniques.

Animals

Development of uterine adenomyosis after treatment with dopamine antagonists in mice.

Development of uterine adenomyosis was studied in SHN mice treated with psychotherapeutic drugs, sulpiride and perphenazine, and gastroenteric drug, metoclopramide, which act as dopamine antagonists to increase prolactin release from the pituitary gland. Administration of these drugs twice daily for 40-70 or 40-90 days of age induced an elevation in serum level of prolactin. Furthermore, the treated mice showed a prolongation of metestrous plus diestrous phase and a high incidence of uterine adenomyosis compared with vehicle-treated control mice. These results indicate that hyperprolactinemia produced by continuous treatment with psychotherapeutic and gastroenteric drugs is responsible for the occurrence of irregular estrous cycles and the genesis of uterine adenomyosis in mice.

Animals

Hyperoxia prolongs the aminoglycoside-induced postantibiotic effect in Pseudomonas aeruginosa.

The objective of this study was to determine whether hyperoxia enhances aminoglycoside activity against Pseudomonas aeruginosa. The existence of tobramycin-oxygen synergy was determined by using the in vitro postantibiotic effect (PAE). P. aeruginosa strains were incubated for 1 h in medium containing tobramycin at four times the MIC in the following gas mixtures: normoxia (21% O2), hyperoxia (100% O2, 101.3 kPa), or hyperbaric oxygen (100% O2, 274.5 kPa). Tobramycin was removed after 1 h and bacteria were incubated under normoxic conditions; growth rates were measured for 5 h. Exposure of three P. aeruginosa strains to hyperoxia prolonged the PAE of tobramycin approximately twofold compared with the PAE after exposure to normoxia (P less than 0.05). Exposure of P. aeruginosa ATCC 27853 to tobramycin and hyperbaric oxygen prolonged the time required for bacteria to increase 1 log10 CFU/ml compared with the time after exposure for this increase to occur in tobramycin-treated, normoxic or hyperoxic groups (P less than 0.02). Pulse-chase labeling of bacteria with L-[35S]methionine, immediately after removal of tobramycin, showed that protein synthesis rates were decreased compared with those in controls (P = 0.0001). Moreover, in tobramycin-treated groups, hyperoxia and hyperbaric oxygen induced 2- and 16-fold decreases, respectively, in protein synthesis rates compared with normoxia; these results did not achieve statistical significance. In the absence of tobramycin, hyperoxia increased bacterial growth (134%; P less than 0.01) and protein synthesis (24%; not significant) compared with normoxia. Hyperbaric oxygen, however, delayed the growth recovery of bacteria (P less than 0.05). We conclude that hyperoxia enhances the bacteriostatic effects of tobramycin in a synergistic manner.+

Anti-Bacterial Agents

Predictive value of family history in detecting hypercholesterolemia in predominantly Hispanic adolescents.

Plasma levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were obtained in 110 senior high school students who were predominantly Hispanic. Results were compared with family history of premature coronary heart disease or hypercholesterolemia. The level of high-density lipoprotein cholesterol was significantly lower in Hispanic adolescents than in non-Hispanics (P less than 0.05). A positive family history was found in 22% of the subjects. Only 25% of the students with high levels of total cholesterol had a positive family history. The positive predictive value of family history for a high level of total cholesterol was only 38%. These results suggest that adolescents should be screened for hypercholesterolemia regardless of a positive family history.

Adolescent

Differences in blood pressure levels obtained by auscultatory and oscillometric methods.

Levels of blood pressure measured by the conventional auscultatory method were compared with those measured by the Dinamap Monitor (Dinamap Monitor 1846 SX, Critikon Inc, Tampa, Fla), an oscillometric device. Triplicate measurements were obtained by the two methods 10 to 15 minutes apart in 381 seated fifth-grade children, ages 10 to 13 years. The width of the air bladder of the blood pressure cuff was selected to be 40% to 50% of the circumference of the upper arm. The mean systolic and diastolic pressures (at the fourth phase of Korotkoff sounds) by the auscultatory method were 6.4 mm Hg lower and 8.7 mm Hg higher than the oscillometric systolic and diastolic blood pressures, respectively. The findings of this study suggest that published normative levels of auscultatory blood pressure may be inappropriate as a standard when blood pressure measurement is obtained by the Dinamap Monitor. Until a new set of normative Dinamap blood pressure levels becomes available, one should use equations (A = 12.8 + 0.82D for systolic, and A = 34.3 + 0.54D for diastolic blood pressures at the fourth phase of Korotkoff sounds, where A is auscultatory blood pressure and D is Dinamap blood pressure) to predict auscultatory blood pressures before Dinamap blood pressures are compared with normative auscultatory blood pressure levels.

Adolescent

Immunocytochemical localization of the subunits of glycoprotein hormones (LH, FSH, and TSH) in the bullfrog pituitary gland using monoclonal antibodies and polyclonal antiserum.

Using beta and alpha subunits of bullfrog follitropin (FSH) III (pI 6.2), which were highly purified by HPLC, we generated three monoclonal antibodies (MCAs) to FSH beta subunit (FSH beta) and six to FSH alpha subunit (FSH alpha). They were produced by hybridomas derived from the myeloma X63.Ag8.653 and spleen lymphocytes from mice immunized with each subunit. Non-competitive binding tests revealed that one of the MCAs against FSH beta (BF3B25) bound strongly to intact FSH and its beta subunit, but not FSH alpha, lutropin (LH), LH alpha, and LH beta. The immunoblotting results also showed a similar immunological specificity for BF3B25. Cross-reactivity of bullfrog FSH against BF3B25 was 19.4%, when compared with FSH beta in the competitive inhibition assay system. On the other hand, noncompetitive binding tests and immunoblotting results showed that one of the MCAs against FSH alpha (BF3A20) bound strongly to intact LH and FSH and their alpha subunits, but not their beta subunits. The inhibition curves obtained using the alpha subunits of LH and FSH were similar. In the sexually mature bullfrog pituitary, immunoreactive FSH cells stained with MCA BF3B25 were distributed throughout the pars distalis, except for the rostral region, and were polygonal in shape, with well-developed cytoplasm. With respect to distribution and histological characteristics, the immunoreactive LH cells were very similar to the immunoreactive FSH cells when consecutive sections were stained with LH beta-specific MCA (BL4B11). However, immunoreactive TSH cells, revealed by anti-human TSH beta serum, formed clusters in the ventrocentral region of the pars distalis. In young adult pituitary, almost all of the gonadotrophs showed the coexistence of FSH and LH, but some gonadotrophs contained only FSH. The number of immunoreactive alpha-subunit cells stained by BF3A20 was always higher than the sum of the numbers of cells stained by the three beta-subunit-specific antibodies.

Animals

Binding of Clostridium botulinum type B toxin to rat brain synaptosome.

Purified toxin and its subunits from Clostridium botulinum type B were labeled with 125iodine and binding of them to rat brain synaptosomes was studied. Labeled toxin and heavy chain were shown to bind to synaptosomes and there was no significant difference in the molar quantity of bound toxin and heavy chain at several concentrations of synaptosomes, whereas labeled light chain did not bind to synaptosomes. The binding of labeled heavy chain to synaptosomes was inhibited by unlabeled toxin and heavy chain to a similar degree as that of labeled toxin. The binding of labeled toxin and heavy chain to synaptosomes were inhibited by a monoclonal antibody which is specific for the heavy chain.

Animals

Primary sequence and heterologous expression of nuclear pore glycoprotein p62.

The major nuclear pore protein p62 is modified by O-linked N-acetylglucosamine and functions in nuclear transport. We have cloned, sequenced, and expressed the full-length rat p62 cDNA. The rat p62 mRNA is 2,941 nucleotides long and encodes a protein of 525 amino acids containing 30% serine and threonine residues. The amino acid sequence near the amino-terminus contains unique tetrapeptide repeats while the carboxy-terminus consists of a series of predicted alpha-helical regions with hydrophobic heptad repeats. Heterologous expression of rat p62 in African Green Monkey Kidney COS-1 cells and CV-1 cells was detected using a species-specific antipeptide serum. When transiently expressed in COS-1 cells, rat p62 binds wheat germ agglutinin and concentrates at the spindle poles during mitosis. In CV-1 cells cotransfected with rat p62 cDNA and SV40 viral DNA, rat p62 associates with the nuclear membrane without interfering with the nuclear transport of SV40 large T antigen. The ability to express p62 in tissue culture cells will facilitate analysis of the role of this pore protein in nuclear transport.

Amino Acid Sequence

Normative oscillometric blood pressure values in the first 5 years in an office setting.

We measured blood pressure (BP) and heart rate in 1554 healthy infants and children aged 2 weeks to 5 years using an oscillometric device, to establish normative values in this age group. The BP cuff width was selected to be 40% to 50% of the circumference of the upper arm. Triplicate measurements of BP and heart rate were obtained in the waiting room of pediatricians' offices and well-baby clinics before the patients were examined by the physician or nurse. Three readings were possible in 87% of the infants less than 3 years of age and in all children 3 years of age and older. The average BP value (systolic/diastolic [mean]) increased rapidly from the 2- to 3-week value of 78/47 (59) mm Hg to the 1- to 5-month value of 95/60 (74) mm Hg. No subsequent increase in BP occurred until 2 years of age (96/56 [71] mm Hg) when systolic and mean pressures started to increase at an average annual rate of 2 mm Hg for systolic pressure and 1 mm Hg for mean pressure until reaching the 5-year value of 104/58 (75) mm Hg. Diastolic pressure did not increase from 1 month to 5 years of age. Heart rate decreased with increasing age from the 2- to 3-week value of 153 to the 5-year value of 97 beats per minute. There was no difference in BP and heart rate values between boys and girls or among ethnic groups over the age ranges studied. Considering the high success rate in obtaining BPs in infants and small children, it appears that BP should be determined routinely, regardless of the age of the patients, when an oscillometric device is available.

Blood Pressure

Hyperoxia and the antimicrobial susceptibility of Escherichia coli and Pseudomonas aeruginosa.

We have tested the ability of hyperoxia (98% O2-2% CO2 at 2.8 atmospheres absolute [ca. 284.6 kPa]) to enhance killing of Escherichia coli (serotype O18 or ATCC 25922) by nitrofurantoin, sulfamethoxazole, trimethoprim, gentamicin, and tobramycin. We have also looked for interactions between hyperoxia and the aminoglycosides against Pseudomonas aeruginosa ATCC 27853. Hyperoxia significantly enhanced bacteriostatic activity of nitrofurantoin and trimethoprim as measured by MIC testing. The possibility exists that these effects might be due to the method required to tests MICs under hyperoxic conditions rather than to the effect of hyperoxia itself. In addition, hyperoxia enhanced killing of bacteria by trimethoprim as measured by MBC testing. Hyperoxia decreased numbers of E. coli by 1.3 log10 and P. aeruginosa by 2.7 log10 in cation-supplemented Mueller-Hinton broth medium. The bacteriostatic effects of hyperoxia did not affect MICs of gentamicin or tobramycin. The lack of interaction between hyperoxia and gentamicin or tobramycin was confirmed by determining the number of viable bacteria remaining after 24 h of exposure to hyperoxia by using a pour plate method. We conclude that hyperoxia potentiates the antimicrobial activity of the reduction-oxidation-cycling antibiotic tested (nitrofurantoin) and of one of the antimetabolites tested (trimethoprim). Hyperoxia does not enhance the bactericidal effects of gentamicin and tobramycin, which require oxidative metabolism for transport into bacterial cells.

Anti-Bacterial Agents

Normative arm and calf blood pressure values in the newborn.

Indirect BP measurement was obtained in the right upper arm in 219 healthy newborn infants with the Dinamap monitor and was compared with values obtained from the calf to establish normative BP values and to help establish a diagnosis of hypertension and coarctation of the aorta in the newborn. There were 174 Mexican-Americans (79.5%), 33 whites (15.0%), and 12 blacks (5.5%). The width of the BP cuff was selected to be 0.4 to 0.5 times the circumference of the extremities. Three supine position readings of BPs and heart rate were obtained from each site and were averaged for statistical analyses. Mean arm BP values (+/- SD) of the neonate less than 36 hours of age were 62.6 +/- 6.9/38.9 +/- 5.7 mm Hg (48.0 +/- 6.2 mm Hg). Neonates older than 36 hours had slightly but significantly (P less than .05) greater values (4 to 6 mm Hg) than did infants younger than 36 hours of age. Active neonates had values 6 to 10 mm Hg greater than quiet neonates (P less than .05). BP values in the calf obtained with the same-sized cuff were almost identical with those obtained from the arm. Differences in consecutively obtained arm and calf BPs (arm values minus calf values) were 1.1 +/- 7.7 mm Hg systolic, -0.01 +/- 6.2 mm Hg diastolic, and 0.9 +/- 6.9 mm Hg mean pressures. Mean heart rate (+/- SD) of neonates less than 36 hours of age was 129.4 +/- 13.2 beats per minute and that of neonates older than 36 hours of age was 139.4 +/- 14.1 beats per minute.(ABSTRACT TRUNCATED AT 250 WORDS)

Arm