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Biomedical subjects

Y Lee

Publications and source records attributed to Y Lee.

At least 451 records · Page 25Linked to original sources

Presence of sex difference of cytochrome P-450 in the rat preoptic area and hypothalamus with reference to coexistence with oxytocin.

Localization of female type cytochrome P-450 (F1) in the preoptic area and hypothalamus of the rat was examined immunocytochemically using antiserum against purified hepatic P-450 (F1). This antiserum recognizes both P-450 (F1) and P-450 (M3). Western immunoblotting using the antiserum demonstrated that female rat brain contains P-450 (F1) but not P-450 (M3), since microsomes from the brain and liver displayed only one immunoreactive band at 50 kD, coinciding with that of P-450 (F1) purified from female rat liver. On the other hand, the male brain has P-450 (M3) but not P-450 (F1), as liver- and brain-derived microsomes produced single band at 49 kD, which represents a mol. wt. identical to that of P-450 (M3) extracted from male rat liver. These results indicate that P-450 (F1)-like immunoreactivity (LI) occurs in the female rat brain, while P-450 (M3)-LI takes place in the male rat brain. Immunocytochemical analysis further demonstrated the detailed cellular localization of these two P-450-LIs in the preoptic area and hypothalamus of female and male rats. Localization of P-450 (F1)-LI in the female rat hypothalamus resembled that of P-450 (M3)-LI in the male rat hypothalamus. Magnocellular neurosecretory neurons in the paraventricular nucleus and supraoptic nucleus were labeled and were found to contain oxytocin but lack vasopressin when serial sections of these areas were analyzed. In addition, groups of immunoreactive cells were seen in the median preoptic nucleus, medial and lateral preoptic area, caudal portion of the bed nucleus of the stria terminalis, lateral hypothalamus at the level of the paraventricular nucleus, periventricular zone from the preoptic area to the paraventricular nucleus, and parvocellular portion of the paraventricular nucleus.

Animals↗

Electrophysiological identification of a pathway from the septal area to the medial amygdala: sensitivity to estrogen and luteinizing hormone-releasing hormone.

Medial amygdala neurons responsive to electrical stimulation of the medial septal area were electrophysiologically identified in ovariectomized, urethane-anesthetized female rats. Peristimulus time histograms were collected and used to define the orthodromic response. The action of iontophoretically applied luteinizing hormone-releasing hormone (LHRH) and an LHRH fragment, Ac-LHRH5-10, on the activity of orthodromically responsive neurons was tested. Of a total of 187 neurons recorded, 119 were identified as orthodromically responsive. Three types of orthodromic responses were observed: excitatory, inhibitory, and complex. Priming the animals with 5 micrograms estradiol benzoate (EB) 48 hr prior to recording had no effect on the overall number of neurons responding to septal area stimulation, but EB priming did significantly reduce the percentage of orthodromically excited neurons. The firing rate of the majority of amygdala neurons responsive to septal area stimulation was not affected by iontophoretically applied LHRH (59 of 76) or LHRH fragment (41 of 65). In some cases, application of LHRH (10 of 76) or Ac-LHRH5-10 (12 of 55) produced a change in neuronal firing that was similar in direction to the orthodromically evoked response. When applied during the collection of peristimulus time histograms, both peptides were also able to modulate the orthodromically evoked response (five of 18 cells tested with LHRH and three of 14 cells tested with Ac-LHRH5-10). The results demonstrate a large projection from the septal area to the amygdala, one component of which is altered by estrogen priming.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗

Transient expression of somatostatin mRNA in the auditory system of neonatal rat.

Postnatal changes of preprosomatostatin mRNA expression in the rat auditory system were examined using in situ hybridization histochemical techniques. It was found that during postnatal days 1 and 2 most of the neurons in the dorsal and ventral cochlear nuclei, and large numbers of neurons in the inferior colliculus, paralemniscal nucleus, and lateral lemniscal nucleus, expressed somatostatin mRNA with a strong intensity. During postnatal development a marked decrease in the number and intensity of neurons expressing somatostatin mRNA was seen. These findings suggested that somatostatin was actively produced in the cochlear nuclei at a very early stage but that production later became reduced or ceased during postnatal ontogeny.

Aging↗

Clinicopathological differences between early-onset and late-onset sepsis and pneumonia in very low birth weight infants.

We performed clinicopathological studies on early-onset sepsis (5 infants, less than 72 hours of life, EOS) and late-onset sepsis (15 infants, greater than 72 hours, LOS) of very low birth weight, less than 1500 g (VLBW). In EOS, the clinical features mimic the respiratory distress syndrome and hematological changes were not observed. The lungs showed slight interstitial pneumonia with structural immaturity, hyaline membranes, hemorrhage, and minimal infiltration by polymorphonuclear neutrophils (PMNs). The pathogen was group B streptococcus or weakly gram-negative bacilli. In LOS, pneumonia proceeded to sepsis and neutropenia with elevated numbers of circulating immature neutrophils, and increased levels of C-reactive protein were observed at the onset of sepsis. Severe pneumonia with infiltration of numerous PMNs and bacterial colonies and polymicrobial infection by nosocomial pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa were common. The thymus and spleen weights varied but retained normal structure in EOS. The thymus was depleted of lymphocytes, and the spleen was hypertrophic but poorly reactive against infection in LOS. The pathogenesis of EOS is regarded as being more closely correlated with lung immaturity and circulatory disorder in early life, whereas that of LOS is associated with immunological defenses of the host, potency of the pathogens, and terminal multiple organ failure.

Blood Cell Count↗

[Does flumazenil antagonize the anesthetic effect of ketamine, etomidate or thiopental?].

The effect of flumazenil, a benzodiazepine antagonist, was assessed in a random, double-blind clinical study in which each of the four groups of surgical outpatients comprising 20 in each was given either ketamine 100 mg (K), etomidate 20 mg (E), thiopental 300 mg (T) or flunitrazepam 4 mg (F) for induction of anesthesia. On emergence, patients in each group were randomly given 2cc of either 2 coded solutions, one of which contained 0.2 mg flumazenil and the other of which was normal saline. Following injection of coded solution, all patients were assessed at 0, 5, 15, 30, 60 and 120 min for wakefulness. All 10 patients of group F who received flumazenil were alert and able to recall at 5 min, whereas in group T this was noted from 15 to 30 min. Patients of group E and K responded alike in a manner as of those who received normal saline placebo with onset of wakefulness at 30 and 60 min respectively. These results confirm that flumazenil antagonizes flunitrazepam (within 5 min) and also indicate that the antagonizing effect occurs 30 min following injection for thiopental, suggestive of some cross-reactivity between these two drugs.

Adult↗

[The effect of epidural anesthesia on tourniquet pain: a comparison of 2% lidocaine and 0.5% bupivacaine].

The incidence of tourniquet pain was evaluated in two groups of patients with 20 each undergoing orthopedic surgery of the lower extremities during epidural anesthesia using plain solution of either 2% lidocaine or 0.5% bupivacaine. The drugs were administered in a randomized fashion. Measurement of the levels of sensory loss to pinprick and incidence of tourniquet pain were made by blind-trust. The maximum analgesia level, time between 1st injection and onset of pain, time between tourniquet inflation and onset of pain were recorded similarly in both groups of patients. The incidence of tourniquet pain was significantly greater in patients given 2% lidocaine (40%) than in patients given 0.5% bupivacaine (10%). The incidence of pain was not related to the time of tourniquet inflation, because patients in the bupivacaine group had a significant longer duration of tourniquet inflation than did patients in the lidocaine group. The incidence of pain was also not related to tachyphylaxis, because 7 of 8 patients who complained tourniquet pain in lidocaine group received less than 3 injections for maintenance of analgesia when tourniquet pain started. In summary, it is apparent that tourniquet pain occurs less frequently when bupivacaine is employed for epidural anesthesia as compared to lidocaine.

Adult↗

Single copies of HIV proviral DNA detected by fluorescent in situ hybridization.

A fluorescent in situ DNA hybridization assay employing a biotinylated DNA probe was used to visualize single copies of human immunodeficiency virus (HIV) proviral DNA in the nuclei and metaphase chromosomes of infected cells. In clonal cell lines that contain either one or two copies of proviral DNA, the efficiency of detection of individual loci of proviral DNA was 57% to 78%. Only 1% of uninfected control cells exhibited a false-positive signal. HIV proviral DNA could be accurately identified in mixed populations comprised of only 5% infected cells. Thus, this assay could be used to identify cells that harbor HIV proviral DNA and to monitor the status of proviral DNA throughout the course of HIV infection.

Cell Line↗

Immunological identification of 1,25-dihydroxyvitamin D3 receptors in human promyelocytic leukemic cells (HL-60) during homologous regulation.

Immunological techniques were utilized to detect 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) receptor levels and to characterize physical/chemical changes in receptors in human promyelocytic leukemic cells (HL-60) during continuous exposure to hormone. The monoclonal antibody (IVG8C11) raised against the porcine intestinal 1,25-(OH)2D3 receptor immunoprecipitated quantitatively 1,25-(OH)2D3 receptors in nuclear extracts from HL-60 cells. The highly enriched immunoprecipitated receptors were electrophoresed on sodium dodecyl sulfate-polyacrylamide gels and transferred to polyvinylidene difluoride membranes, which were probed with 125I-labeled IVG8C11. The basal receptor from the cells treated with 1,25-(OH)2D3 for 2 h was detected as a single form at 53 kDa. Moreover, receptors were shown to be up-regulated at 12 h and down-regulated at 48 and 72 h in the continuous presence of hormone as evidenced by the ratio of density of the bands, 1.0 (2 h):4.2 (12 h):1.2 (48 h):0.9 (72 h), as measured by laser scanning densitometry. The up- and down-regulated receptors were also detected as single forms and had the same molecular mass as the basal receptor. Therefore, the data presented here strongly support the hypothesis of homologous regulation of 1,25-(OH)2D3 receptors in intact human target cells.

Antibodies, Monoclonal↗

Sites of initiation and pausing in the Escherichia coli rnpB (M1 RNA) transcript.

DNA sequences affecting the transcription of the Escherichia coli rnpB transcript encoding the catalytic M1 RNA subunit of RNase P have been analyzed. Previous work (Motamedi, H., Lee, Y., and Schmidt, F.J.) (1984) Proc. Natl. Acad. Sci. U. S. A. 81, 3959-3963) identified S1 nuclease protection products corresponding to transcripts originating upstream of the M1 RNA gene. Sequence analysis of the upstream region of rnpB identified three regions homologous to the E. coli consensus promoter sequence. In the present work, analysis of in vitro transcription products by S1 nuclease mapping indicated that all three promoter homologies were capable of directing transcription. The nearest promoter, P-1, was approximately 100 times more active than either of the upstream homologies P-2 and vivo experiments, wherein the three promoter homologies preceding rnpB were cloned into the galactokinase (GalK) expression vector pKO100. The promoter homology nearest to the M1 RNA gene directed the synthesis of GalK above background. The upstream promoter homologies did not direct the synthesis of GalK at a level greater than 1% of transcription from P-1. Deletion of the upstream homologies did not affect transcription from P-1. It was concluded that P-1 is responsible for essentially all M1 RNA transcription in vivo. Single-round transcription experiments in vitro detected strong NusA-independent transcriptional pausing at nucleotides +118 and +121 of the rnpB transcript, with a half-life of 27 s when concentrations of NTPs were near the average Km for elongation. Pausing at these points was eliminated by substitution of ITP for GTP in the transcription mixture. This suggests that pausing is dependent on transcript secondary structure. The position of pausing corresponds to that of a dual stem and loop structure of M1 RNA which has recently been proposed on the basis of phylogenetic sequence analysis.

Base Sequence↗

Zinc acetate pretreatment ameliorates cisplatin-induced Sertoli cell dysfunction in Sprague-Dawley rats.

The present study was undertaken to determine if prior administration of zinc acetate (ZnAc) or copper sulfate (CuSO4) could prevent pituitary, Leydig, or Sertoli cell dysfunction subsequent to cisplatin administration in adult Sprague-Dawley rats. Animals were given cisplatin at a dose of 2 mg/kg daily for 5 days, with or without the i.p. administration of ZnAc (6 mg/kg per day) or CuSO4 (5 mg/kg per day), beginning 5 days prior to and continuing through the administration of cisplatin. Control animals were given vehicle, ZnAc1, or CuSO4. Animals were sacrificed 1 week after the initial cisplatin injection. Cisplatin administration resulted in suppressed serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels as well as a 77% reduction in serum testosterone and an 82% reduction in testicular testosterone. The concomitant administration of either ZnAc or CuSO4 did not result in a significant difference relative to animals receiving cisplatin alone, although administration of both cations alone significantly reduced testicular testosterone content. Serum androgen-binding protein (ABP) was not significantly lowered in any treatment group. There was a marked reduction of 57% in testicular ABP content relative to control values subsequent to cisplatin administration. This reduction was partially prevented by ZnAc treatment: the testicular ABP concentration was only 15% lower than that in controls (not significant). Since the cisplatin-induced reduction in serum FSH was not altered by ZnAc pretreatment, we conclude that the near normalization of testicular ABP content may be evidence of improved Sertoli cell function. In contrast, cisplatin-induced decreases in the serum gonadotropins and testicular androgens were not lessened by pretreatment with either cation. Further studies may be warranted to determine whether ZnAc pretreatment has a beneficial effect on spermatogenesis during cisplatin treatment.

Acetates↗

Characterization of cis-platinum-induced Sertoli cell dysfunction in rodents.

The present study examined the effects of dosage and frequency of cis-platinum administration on various aspects of Sertoli cell function and its correlation with the status of spermatogenesis in rats 1 and 9 weeks after the initial drug administration. Adult male Sprague-Dawley rats were administered cis-platinum (10 mg/kg) intraperitoneally as a single dose or as five daily doses of 2 mg/kg. Electron microscopic observation of testicular tissues fixed in the presence of lanthanum revealed that cis-platinum administration resulted in leakage of the Sertoli cell tight junctions. This occurred as early as 24 hr after the five daily injections, and persisted at least 40 days. Testicular androgen-binding protein (ABP) content was not significantly affected by either treatment regimen after 1 or 9 weeks of recovery. On the other hand, serum ABP values were significantly elevated after 9 weeks of recovery. In addition, the increased sodium and decreased potassium concentrations in seminiferous tubular fluid noted in cis-platinum-treated animals were also indicative of abnormal Sertoli cell secretory function. Degeneration of spermatogenic cells was noted as early as 5 days after the last drug administration; and partial restoration of spermatogenesis was noted after 40 days of recovery. We conclude that in rats both morphological and biochemical properties of Sertoli cells are affected by cis-platinum administration. These changes in Sertoli cell function may be responsible for the cis-platinum-induced impairment of spermatogenesis in these animals.

Androgen-Binding Protein↗

An allometric analysis of the U.S. urban system: 1960-80.

"In the present study the allometric equations for urban places in the [United States] are derived and interpreted. Data on the area and population size of the urbanized area (as defined in the U.S. Census) for 1960, 1970, and 1980 are fitted to the allometric equation. The data set for each of the three time periods is further disaggregated by population-size class (seven classes) and by region (nine regions in total). The results of the analysis are interpreted with reference to works of allometric growth in the biology and urban growth literature."

Americas↗

Influence of drugs on albumin and bilirubin interaction.

Twenty-eight drugs, including cephem antibiotics and anti-inflammatory agents currently used or considered potentially useful in neonatal intensive care nurseries in Japan, were examined to determine their influence on albumin and bilirubin interaction by means of a glucose oxidase - peroxidase method, using an automated analyzer (Arrows) for unbound bilirubin (U.B.). The apparent binding constant for drugs to the high-affinity site on albumin (KD) was determined. Of cephem antibiotics, latamoxef sodium (LMOX) and cefazolin sodium (CEZ) were found to displace bilirubin from albumin (KD = 5.9 x 10(3) M-1 and 4.5 x 10(3) M-1, respectively) as strongly as Na salicylate (KD = 6.8 x 10(3) M-1). Mephenamate and indomethacin, which are used for medical closure of patent ductus arteriosus in premature infants, were also found to be stronger bilirubin displacers (KD = 1.3 x 10(5) M-1 and 1.2 x 10(5) M-1, respectively) than sulfisoxazole (KD = 1.6 x 10(4) M-1). Maximal displacement factors (MDF's) were also estimated in reference to protein binding (%) and effective serum concentration (M) of each drug in human adults. Of these drugs, mephenamate showed a higher risk of bilirubin displacement (MDF = 3.79) than sulfisoxazole (MDF = 2.58) and LMOX had a higher risk of displacement (MDF = 1.97) than Na salicylate (MDF = 1.85). On the other hand, indomethacin and CEZ showed minimal effects on displacement at therapeutic levels (MDF = 1.03 and 1.00, respectively). At therapeutic serum levels, mephenamate and LMOX may possess the potential for displacing bilirubin from albumin and increasing the risk of bilirubin encephalopathy, in a manner similar to sulfisoxazole.

Albumins↗

Incidence and survival of cancer in Kangwha County (1983-1987).

To measure incidence and survival rates of cancer in Kangwha County, 663 cancer patients registered in the Kangwha County Cancer Registry Program for the past 5 years (1983-1987) were analyzed. The average annual cancer incidence rate per 100,000 population was 183.0 in males and 99.5 in females. The common cancers were stomach (37.3%), lung (14.8%), and liver cancer (11.1%) in males and stomach (25.6%), cervix uteri (20.9%), and liver cancer (9.7%) in females. The median survival times of all cancer patients after diagnosis and onset of the first symptom were 8.4 +/- 0.8 months and 15.0 +/- 1.1 months respectively. Female cancer patients survived significantly longer than male cancer patients. The median survival times of the stomach, lung, and liver cancer in males were 7.7 +/- 0.9, 4.9 +/- 0.9, and 2.3 +/- 0.4 months respectively. In females, the median survival times of the stomach and liver cancer patients were 9.2 +/- 1.5 and 2.5 +/- 0.5 months. The 5 year survival rate of cervical cancer was 67.1%. Those cancer patients who received anticancer therapy survived significantly longer than cancer patients without treatment.

Female↗

Microcholangiography. Normal microbiliary system and its alteration after extrahepatic bile duct obstruction.

The authors used microcholangiography to demonstrate the feasibility of the technique and the features of the normal and the obstructed biliary systems. Furthermore, they attempted to explain the pathophysiology of cholangiography-related septicemia with this technique. Extrahepatic bile ducts (EHBD) of 40 rabbits were ligated, and microcholangiography was carried out with infusion of barium suspension immediately as well as one, three, and five days after ligation. Microradiographic technique was used and the findings were correlated with histopathologic features. The intrahepatic microbiliary system such as interlobular bile ducts and ductules were well visualized. After EHBD ligation, ductules were tortuously dilated. The histologically observed ductular proliferation in many hepatobiliary diseases could be attributed in part to the tortuosity of bile ductules, particularly when biliary obstruction is present. Regurgitation of barium into hepatic sinusoids was demonstrated in 36 rabbits (90%) and probably was caused by rupture of interlobular bile ducts and ductules.

Animals↗

[Clinical efficacy of fluconazole in the patient with pulmonary mycosis].

Fluconazole, a novel triazole antifungal agent, was given orally or intravenously to 10 patients with pulmonary mycosis (7 patients with primary pulmonary cryptococcosis and 3 with pulmonary aspergillosis). Routes of administration were changed in some patients depending on their condition. Two patients from whom foci was removed by surgical operations were excluded from the efficacy assessment. Clinical efficacies in the remaining 8 patients were good in 2 cases and fair in 3 cases of pulmonary cryptococcosis; excellent in 1 case of pneumonia due to Aspergillus; and fair in 1 case and poor in the other case of pulmonary aspergilloma. Side reactions developed in 9 patients who received intravenous drip infusion were nausea or loss of appetite in 3 patients, fever and/or feverish sensation in 3, vascular pain in 1 and diarrhea and eruption in 1. In the patient who reported fever the drug was discontinued and in the patient who complained of pain at the site of injection, dosing was changed to the oral route but was discontinued due to elevated GOT, GPT, Al-P and gamma-GTP. Seven patients who received the drug orally did not report side effects except 2 patients. None of these side effects reported was serious and from the above results, fluconazole was considered to be a useful agent for the treatment of pulmonary mycosis.

Administration, Oral↗

Buthionine sulfoximine-mediated depletion of glutathione in intracranial human glioma-derived xenografts.

D-54 MG, a human glioma-derived continuous cell line growing as subcutaneous or intracranial xenografts in athymic mice, was found to be sensitive to the effects of D,L-buthionine-(SR)-sulfoximine, a selective inhibitor of gamma-glutamylcysteine synthetase. Intraperitoneal administration of one dose of buthionine sulfoximine (BSO, 5 mmol/kg) resulted in depletion of total intracellular glutathione to 57 and 47% of control 12 hr, and 73 and 23% of control 24 hr, after BSO in subcutaneous and intracranial xenografts respectively. Concurrent measurement of total glutathione in the contralateral (non-tumor-containing) cerebral hemisphere in mice bearing intracranial D-54 xenografts demonstrated insignificant depletion of glutathione. Multiple doses of BSO, at 12-hr intervals, resulted in further depletion to 27% (s.c.) and 16.5% (i.c.) of control 12 hr following the final dose of BSO. Quantitative analysis of BSO delivery to xenograft and contralateral brain tissue revealed transfer constants, K1, of 15.8-24.1 x 10(-3) and 2.4 x 10(-3) ml.g-1.min-1 for xenograft and "normal" brain respectively. This highly selective depletion of glutathione in neoplastic tissue versus surrounding non-neoplastic host tissue may have therapeutic implications for the rational use of chemotherapeutic and radiotherapeutic intervention.

Animals↗

Partial prevention of procarbazine induced germinal cell aplasia in rats by sequential GnRH antagonist and testosterone administration.

The present study examined the feasibility of using a combination of gonadotropin releasing hormone antagonist (GnRH-A) and testosterone in the prevention of procarbazine induced germinal aplasia. Daily injections of GnRH-A or vehicle were given to adult male rats for 21 days prior to procarbazine (PCB) administration and continued until 2 days after the second of two doses of procarbazine (200 mg/kg i.p.) given 1 week apart. One group of rats receiving GnRH-A and PCB was given s.c. two 5-cm testosterone capsule (TC) implants (inside diameter, 3.5 mm) immediately following the second dose of PCB. Eight weeks after the last PCB treatment, more than 99% of the seminiferous tubular cross-sections of rats receiving PCB alone were devoid of spermatogenic activity. Spermatogenesis in PCB injected animals receiving GnRH-A pretreatment alone was abortive but was partially preserved when exogenous testosterone was given following PCB administration. At 16 weeks, spermatogenesis was absent in all PCB treated animals and was only observed in less than 1% of the tubular cross-sections of the PCB treated rats receiving GnRH-A pretreatment alone. On the other hand, active spermatogenesis was noted in 68% of the tubular cross-sections, and complete spermatogenesis was noted in four of the five PCB treated rats receiving both GnRH-A pretreatment and subsequent TC implantation. At the time of sacrifice, testicular testosterone concentrations in animals receiving TC implants were below 10% of normal levels, while both serum and testicular testosterone content were increased in PCB treated animals with or without GnRH-A pretreatment. Concomitantly, testicular androgen binding protein content remained suppressed and serum androgen binding protein was elevated, indicating a prolonged defect in Sertoli cell function. These lesions were prevented by GnRH-A pretreatment. The present study demonstrates that GnRH-A pretreatment and subsequent TC implantation resulted in restoration of complete spermatogenesis in adult male rats given a 400-mg/kg cumulative dose of PCB. It is postulated that GnRH-A may ameliorate PCB induced Sertoli cell dysfunction and/or stimulate the number of spermatogonia to provide more proliferating cells ready for repopulation of the germinal epithelium following PCB injury. The differentiation of these spermatogonia was further supported by exogenous testosterone through certain unknown local mechanisms, resulting in the completion of spermatogenesis.

Androgen-Binding Protein↗