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Biomedical subjects

K Kim

Publications and source records attributed to K Kim.

At least 451 records · Page 25Linked to original sources
PubMed1993

Phase II study of taxol, merbarone, and piroxantrone in stage IV non-small-cell lung cancer: The Eastern Cooperative Oncology Group Results.

BACKGROUND: Patients with metastatic (stage IV) non-small-cell lung cancer usually have a poor prognosis and disease refractory to chemotherapy. Three new agents--taxol, merbarone, and piroxantrone--have shown promising antitumor treatment in vitro and in animals. Taxol is an antimicrotubular agent that interferes with mitosis during cell division. Merbarone, a conjugate of thiobarbituric acid and aniline, is a topoisomerase II inhibitor, which thus inhibits DNA synthesis and tumor growth. Piroxantrone, an anthracenedione derivative, is a DNA intercalating agent that has shown potent antitumor activity in animal studies. PURPOSE: Our randomized phase II study was designed to evaluate the efficacy and toxicity of these agents in the treatment of stage IV metastatic non-small-cell lung cancer. METHODS: Eligible patients (119) were randomly assigned to receive one of the three treatments given every 3 weeks: 250 mg/m2 taxol by a 24-hour intravenous infusion, 1000 mg/m2 merbarone by continuous intravenous infusion through a central catheter daily for 5 days, or 150 mg/m2 piroxantrone by intravenous infusion over 1 hour. Patients had received no chemotherapy. Response and toxicity were evaluated every 3 weeks. RESULTS: Twenty-five patients were randomly assigned to receive taxol, 47 to receive merbarone, and 47 to receive piroxantrone. One of 44 assessable patients (2.3%) treated with piroxantrone had a complete response. Rates for partial response were 20.8% (five of 24 patients) and 5.7% (two of 35) for assessable patients treated with taxol or merbarone, respectively. One-year survival rates were 41.7%, 21.6%, and 22.6%, and median survival times were 24.1, 19.9, and 29.3 weeks for taxol, merbarone, and piroxantrone, respectively. These differences were not statistically significant, but this study was not designed to compare survival. In general, toxicity was manageable. With premedication, no anaphylaxis was observed with taxol. The most common toxic effects were leukopenia with taxol or piroxantrone treatment and thromboembolic complications with merbarone. Death directly related to treatment occurred in 4% (one patient), 11.4% (four), and 5% (two) of the assessable patients receiving taxol, merbarone, and piroxantrone, respectively. Cardiotoxicity and neurotoxicity occurred only occasionally in all three arms. CONCLUSION: On the basis of the response rate (20.8% partial response) and 1-year survival rate (41.7%), taxol is an active agent for the treatment of metastatic non-small-cell lung cancer. Merbarone and piroxantrone are relatively inactive. IMPLICATIONS: Further study of taxol is warranted. In future studies, taxol should be combined with other agents, and granulocyte colony-stimulating factor should be used to ameliorate myelosuppression.

Adult↗
PubMed1993

Changes in the activities of steroidogenic enzymes during the development of ovarian follicles in Rana nigromaculata.

Earlier studies showed that the predominant steroid (estradiol [E2], testosterone [T], progesterone [P4]) secreted by in vitro cultured amphibian (Rana nigromaculata) ovarian follicles varied with their size. E2 was mainly produced by medium-sized follicles, T by intermediate-sized follicles, and P4 by the largest follicles. Experiments were carried out to ascertain whether the activities of steroidogenic enzymes changed during follicle development and were responsive to gonadotropic stimulation. Enzyme activities were measured indirectly by monitoring conversion of exogenously added substrates to products during in vitro culture of isolated follicles. Different stage follicles were cultured in the presence or absence of frog pituitary homogenate (FPH, 0.1 pituitary/2 ml) and/or various steroid precursors (25-200 ng/2 ml). Amounts of E2, T, androstenedione (AD), 17 alpha-hydroxyprogesterone (17 alpha-OHP4), or P4 secreted into the medium were measured by RIA. Exogenous pregnenolone (P5) was converted to P4 by all types of follicles in a dose-dependent manner in the absence of FPH. Addition of FPH markedly enhanced medium levels of P4 in all sized follicles. Highest levels of P4 were presented in cultures containing the largest follicles. Such follicles were much less efficient than intermediate follicles in metabolizing P4 to AD or T. FPH suppressed conversion of exogenous 17 alpha-OHP4 but not androstenedione to testosterone by the largest follicles. Exogenous T was converted to E2 only by medium-sized follicles and FPH had little or no stimulating or inhibiting effect on this process in either medium- or intermediate-sized follicles.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗
PubMed1993

Progesterone inhibits the estrogen-induced prolactin gene expression in the rat pituitary.

The present study examines the inhibitory action of progesterone (P) on prolactin (PRL) gene expression in the anterior pituitary of ovariectomized, estradiol (OVX+E) treated adult rats. A single injection of P (1 mg) was administered s.c. to OVX+E treated rats, and animals were killed at 3, 6, 9, and 36 h following P administration. Northern blot analysis showed that P suppressed the E-enhanced PRL mRNA level at 3, 6, and 9 h, but not at 36 h following P administration. When the second injection of P (1 mg) was given at 30 h after the first P, it again suppressed the E-induced PRL mRNA level, indicating that the inhibitory effect of P may not last until 36 h. The inhibitory action of P was dose-dependent, and the pretreatment of RU486 (100 micrograms/rat), a P receptor antagonist at 1 h before P injection partially restored PRL mRNA level which was inhibited by P. These data indicate that P plays a crucial role in the regulation of PRL gene expression in the rat pituitary.

Animals↗
PubMed1993

Competitive PCR for quantitation of gonadotropin-releasing hormone mRNA level in a single micropunch of the rat preoptic area.

A competitive polymerase chain reaction (PCR) for quantitating gonadotropin-releasing hormone (GnRH) mRNA level in a single micropunch of the rat preoptic area (POA) is described. The POA (600 microns in depth) was micropunched from frozen rat brain slices and used for mRNA isolation using Dynabeads-oligo(dT) magnetic separation technique. The target RNA combined with a synthetic, deletion mutant GnRH cRNA as an internal standard, is co-reverse transcribed, and their cDNAs are subsequently co-amplified by Taq DNA polymerase in the same tube in which the same GnRH primers are used. This PCR protocol is sensitive enough to detect GnRH mRNA level in a single POA micropunch derived from an individual rat. There is a linear increase of the amount of GnRH PCR products as a function of input RNA and of the number of PCR cycles. Addition of mutant GnRH cRNA as an internal standard allows us to quantitate GnRH mRNA level in biological samples and to compensate variations of PCR reaction between samples. Following preoptic treatment with 5'-ADMP, which depletes selectively norepinephrine (NE), GnRH mRNA level was significantly reduced. This simple, yet highly sensitive PCR method appears to be a valuable tool for the study of the cellular and molecular regulation of GnRH gene expression in a variety of experimental models.

Animals↗
PubMed1993

Speed versus accuracy instructions, study time, and the mirror effect.

Attention/likelihood theory is a model of recognition memory designed to explain the mirror effect (Glanzer & Adams, 1985, 1990). The theory and the effect were studied using speed versus accuracy instructions and short versus long exposure of stimuli. Speed versus accuracy instructions during test and short versus long exposure of stimuli during study were used to vary the number of features sampled from stimuli. When the number of features sampled was reduced either by speed instructions or by shorter exposure, recognition performance was impaired. The theory predicts that in such cases, all distances between underlying distributions will contract. That means, moreover, that when recognition accuracy is decreased for old stimuli, it is also decreased for new stimuli. These predictions were supported by the data from three experiments.

Adult↗
PubMed1993

The regularities of recognition memory.

Three regularities in recognition memory are described with supporting data: the mirror effect, the order of receiver operating characteristic slopes, and the symmetry of movement of underlying distributions. The derivation of these regularities from attention/likelihood theory is demonstrated. The theory's central concept, which distinguishes it from other theories, is the following: Ss make recognition decisions by combining information about new and old items, the combination made in the form of likelihood ratios. The central role of the likelihood ratios extends the implications of signal detection theory for recognition memory. Attention/likelihood theory is fitted to data of 2 series of experiments. One series involves yes-no tests and confidence ratings, the other forced-choice experiments. It is argued that the regularities require a revision of most current theories of recognition memory.

Aging↗
PubMed1993

Facilitating prelinguistic communication skills in young children with developmental delay.

Very little research has focused on the development and evaluation of intervention strategies designed to facilitate the acquisition of prelinguistic communication skills. We conducted two experiments to determine the effects of a milieu teaching approach on the acquisition and generalization of specific prelinguistic communication skills. In the first experiment, we utilized this intervention approach within a multiple baseline design to teach prelinguistic requesting, commenting, and vocal imitation to a single subject with Down syndrome and language delay. The results indicated that the intervention approach was effective at facilitating the child's use of these skills within the treatment setting. Therefore, in the second experiment we conducted a more comprehensive analysis of this approach with 4 subjects with mental retardation. Three of these subjects were taught to request, and 1 subject was taught both to request and to comment. The effects were experimentally evaluated with multiple baseline across subjects design. The results indicated that the intervention was effective in eliciting the intervention targets within the training setting for all 4 subjects. All 4 subjects showed evidence of generalization across stimulus materials, setting, teachers, and interaction style. There was also evidence of reciprocal effects on how classroom teachers in the generalization setting interacted with the subjects as a result of changes in the child's communication behavior.

Child, Preschool↗
PubMed1993

Effect of high hydrostatic pressure on the conversion of alpha-connectin to beta-connectin.

The factors affecting the conversion of alpha-connectin to beta-connectin induced by pressurization of muscle were investigated over a pressure range from 100 to 400 MPa by using SDS-PAGE and immunoblot analysis. When muscles were exposed to high pressures, the conversion of alpha-connectin to beta-connectin was the most pronounced at a pressure of 300 MPa, and the appearance of 1,200-kDa peptide accompanied by conversion of alpha- to beta-connectin was observed. Connectin was relatively resistant to degradation under a pressure of 400 MPa. The degradative products of beta-connectin reactive with mAb 2D4 were not observed. The effect of high pressure on connectin in isolated myofibrils was similar to that on connectin in muscle. Addition of leupeptin and E-64 to the isolated myofibrils resulted in the prevention of the degradation of connectin at each stage of the pressurization. The ability of calcium-activated protease (calpain) to hydrolyze connectin from alpha to beta gradually declined with increasing pressure. The results indicate that calpain is responsible for the pressure-induced conversion of alpha- to beta-connectin. The rate of this conversion is probably regulated by the pressure-dependent structural change of alpha-connectin and inactivation of calpain.

Animals↗
PubMed1993

Collagen metabolism during wound healing in rats. The aminoterminal propeptide of type III procollagen in serum and wound fluid in relation to formation of granulation tissue.

The aminoterminal propeptide of type III procollagen (PIIINP) in serum has been shown to correlate with fibrillogenesis, and thus to be a potential direct marker of type III collagen deposition. The aim of the study was to investigate the correlation between changes in serum PIIINP and formation of granulation tissue during pharmacological suppression. Granulation tissue was induced in rats by the implantation of viscose cellulose sponges. Pharmacological suppression was achieved by cyclophosphamide treatment. To distinguish between the isolated effect of cyclophosphamide and the influence of the weight loss caused by treatment, weight loss caused by starvation was investigated. In untreated rats, serum PIIINP and wound fluid PIIINP were related to formation of granulation tissue (serum: r = 0.58, p < 0.05; wound fluid: r = 0.56, p < 0.05). In rats treated with cyclophosphamide, collagen deposition and formation of granulation tissue were markedly reduced, as compared within the untreated rats (6% vs 33%, p = 0.01). Wound fluid PIIINP reflected the sparse collagen deposition (r = 0.48, p < 0.05), whereas serum PIIINP decreased (-35%, p < 0.01) and was not correlated with the formation of granulation tissue. In starved rats, with a weight loss of 8%, formation of granulation tissue, vascular density, and collagen deposition were not reduced. Wound fluid PIIINP reflected the formation of granulation tissue (r = 0.52, p < 0.05), whereas serum PIIINP remained unchanged despite normal formation of granulation tissue. Starvation of rats without implants caused a decrease in serum PIIINP (-33%(-)-48%, p < 0.01). We conclude that during cyclophosphamide treatment and after a moderate weight loss, serum PIIINP is not a valid marker of fibrillogenesis. However, in normal rats with free access to food, changes in serum PIIINP mirror fibrillogenesis. Furthermore, our study provides experimental evidence consistent with the hypothesis that wound fluid PIIINP directly mirrors the local formation of granulation tissue, independent of weight loss and cyclophosphamide treatment.

Animals↗
PubMed1993

A partial blockade of catecholaminergic neurotransmission with 6-hydroxydopamine decreases mRNA level of gonadotropin releasing hormone in the male rat hypothalamus.

Central catecholamines (CA) are known to be involved in the regulation of synthesis and secretion of gonadotropin releasing hormone (GnRH) from the hypothalamus. However, no attempt has been yet made to determine whether CA affects GnRH gene expression. To this end, the effect of 6-hydroxydopamine (6-OHDA), a catecholaminergic neurotoxin, on GnRH mRNA level was examined. Hypothalamic tissues obtained from adult male rats were incubated with medium containing 6-OHDA. To ensure the effect of 6-OHDA on CA depleting action, CA levels in media and in postincubation tissues were determined. Increasing concentrations of 6-OHDA resulted in decrease in norepinephrine (NE) and dopamine (DA) contents in a dose dependent manner. Treatment with 6-OHDA (5 x 10(-4) M produced a time-dependent decrease in NE but not DA, when CA levels in media were determined at 30 min intervals during the incubation period. To determine changes in GnRH mRNA level in response to 6-OHDA treatment in vitro, for 2.5 h total cytoplasmic RNA fractions were isolated from postincubation hypothalamic tissues and used for RNA-blot hybridization with 32P-labeled GnRH riboprobe. A blockade of CA neurotransmission with 6-OHDA (5 x 10(-4) M) significantly reduced GnRH mRNA level by half over its control and internal control (actin mRNA) groups. Northern blot analysis revealed that addition of NE (1 x 10(-6) M) reversed the decreased GnRH mRNA level by 6-OHDA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

NMDA receptor antagonist decreases the progesterone-induced increase in GnRH gene expression in the rat hypothalamus.

We previously reported that GnRH gene expression was enhanced by progesterone (P) in the hypothalamus from ovariectomized and estrogen (OVX+E) treated immature rats. Recent studies indicate that excitatory amino acids may play an important role in the regulation of GnRH secretion and gene expression by steroids. Therefore the present study attempts to examine whether excitatory amino acids are involved in the P-induced GnRH gene expression and release in vitro. MK-801, an NMDA receptor antagonist or CNQX, a non-NMDA receptor antagonist, was administered to OVX+E+P-treated prepubertal female rats. GnRH mRNA was determined by Northern blot hybridization using 32P-labeled antisense RNA, and GnRH release in vitro from the hypothalamic fragments was monitored by GnRH radioimmunoassay. The administration of MK-801 (0.2 mg/kg) for 2 h significantly reduced the P-induced GnRH gene expression and release, whereas CNQX (0.4 mg/kg) had no effect. These results clearly indicate that excitatory amino acids by way of NMDA receptor are involved in the transsynaptic regulation of GnRH gene expression.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1993

Using enteral nutrition formulas.

A review of enteral tube feeding formulations is presented. When choosing an enteral formula product for a patient one must first determine the calorie and protein needs of the patient. Then one must determine the level of gastrointestinal tract function. First ask, to what degree is the small bowel functioning: totally, partially, or not at all? Has the small bowel lost surface area because of atrophy, inflammation, or surgical removal? Is the gut edematous because of hypoalbuminemia or congestive heart failure? Is bowel motility impaired by opioids, anticholinergics, or mechanical ileus? Is digestion limited by pancreatic or bile acid insufficiency? Has absorption been decreased by intestinal ischemia or gastrointestinal bleeding? Decreased surface area, bowel edema, and diminished digestive juices are only partial losses of small bowel function. An elemental formula should be tried first in these situations. Any of the other problems alone or in combination probably preclude the use of the small bowel and the patient will need total parenteral nutrition. If gastrointestinal function is adequate, then other organ failures that result in specific nutrient intolerance must be ruled out. If gastrointestinal function is adequate and no other organ failures preclude the use of a polymeric formula, then one must decide if stress and hypermetabolism are present. Enteral feeding is the preferred method of providing specialized nutrition support. Bowel rest reduces the barrier functions of the gut and malnutrition reduces cell-mediated immunity. The indications and relative contraindications for enteral tube feeding are also reviewed. The rationale for the formula design and the evidence for formula efficacy are presented. Polymeric, elemental, organ-specific, and immune-modulating formulas are discussed. Guidelines for formula selection are suggested.

Enteral Nutrition↗
PubMed1993

IgG deficiency in adults with recurrent respiratory infections.

Total IgA, IgM, IgG, and IgG subclasses were measured in 136 consecutive adults with recurrent respiratory infections. Sinus and chest radiographs were also obtained. IgG antibodies to H. influenzae and tetanus toxoid were determined in 27 immunodeficient subjects. Fifty-eight of the 136 were deficient in some immunoglobulin isotype, three in IgA, three in IgM, and 52 in total IgG or one or more IgG subclasses. The most common IgG deficiencies were single IgG subclass deficiencies, particularly IgG3 or IgG4, and a mild decrease in total IgG (between 450 and 650 mg/dL). In 21/27 subjects with IgG deficiency, the response to booster immunization was blunted, even when IgG1 and IgG2 were normal. Thirty-eight patients were smokers, 37 being > 40 years of age at the onset of respiratory infections. Twenty patients were nonsmokers, 19 being < 40 years of age at the onset. In conclusion, adults with recurrent respiratory infections frequently have some variant of IgG deficiency, often associated with a functional impairment of specific antibody response. Smoking may represent a risk factor for IgG deficiency in adults.

Adult↗
PubMed1992

Percutaneous fenestration of dissecting intima with a transseptal needle. A new therapeutic technique for visceral ischemia complicating acute aortic dissection.

Noncardiac visceral ischemia is a major complication with acute aortic dissection and is caused by obstruction of the major visceral arteries by dissecting intima. Two patients with this condition underwent emergency percutaneous fenestration of dissecting intima, and the blood flow to the lower extremity and kidney was restored. A transseptal needle and peripheral angioplasty balloon catheter were used for fenestration. There were no associated complications in either patient. One patient was treated medically and another had ascending aortic replacement surgery the day after percutaneous fenestration. Clinical follow-up of 10 and 5 months, respectively, revealed good clinical outcomes. Percutaneous fenestration should be considered the treatment of choice for visceral ischemia due to acute aortic dissection.

Aortic Dissection↗