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Biomedical subjects

W K Kim

Publications and source records attributed to W K Kim.

At least 19 recordsLinked to original sources

Contribution of B cell subsets to delayed development of MAIDS in xid mice.

C57BL/6 (B6) mice develop a syndrome of progressive lymphoproliferation and immunodeficiency, murine AIDS (MAIDS), when infected with an etiologic replication-defective virus termed BM5def. Induction of MAIDS requires the presence of CD4+ T cells and B cells. B6 mice with altered conventional B cell function and a deficit in CD5+ B cells due to the xid mutation develop disease with a greatly prolonged latency. The association of this mutation with resistance to MAIDS was confirmed in studies of P.xid mice. To test the hypothesis that conventional B cells are required for rapid induction of disease, B6.xid mice were injected with spleen cells from nude mice or were given bone marrow from aged donors. Both sets of recipients developed advanced disease by 10 weeks post infection, suggesting that resistance to MAIDS in xid mutants may be due to effects of B cells other than the CD5+ subset.

Agammaglobulinaemia Tyrosine Kinase

Adult Hirschsprung's disease. Results of the Duhamel's procedure.

Eleven patients with adult Hirschsprung's disease were treated at Seoul National University Hospital (SNUH, 8 cases) and Chosun University Hospital (CUH, 3 cases) between 1985 and 1992. Of the 11 patients, seven were male. The age of the patients ranged from 11 to 30 years, and all presented with chronic constipation and recurrent faecal impactions that required periodic enemas and laxatives. The Duhamel's operation, as a single or staged procedure, was performed in all patients. Levels of aganglionosis in 9 patients were confined to the rectosigmoid colon (82%). There were three major post-operative complications. Two patients developed fistula-in-ano at the anastomotic site, and one patient developed ileus. However, these complications resolved with conservative management. The longterm results were excellent except for one patient who developed impotence. The mean frequency of bowel movements was usually once or twice a day without the aid of other treatments. Our results indicate that Duhamel's operation is a highly acceptable procedure in the management of adult Hirschsprung's disease.

Adolescent

Mechanism of transmission and modulation of renal pain in cats; effect of nucleus raphe magnus stimulation on renal pain.

Initially, when periaqueductal gray (PAG) is electrically stimulated, analgesia is induced, and this phenomenon is called stimulation-produced analgesia. Nucleus raphe magnus (NRM) as well as PAG are known to be the potent analgesic centers. NRM could modulate the nociceptive response of spinal cord neurons through spinally projecting fibers. However, as well as the above analgesic effects have been confined to the somatic pain, it was variable according to species, and the analgesic effect by NRM stimulation on the visceral pain was not yet clarified. In this study the analgesic effect by NRM stimulation on the visceral pain was examined through recording the activities of the dorsal horn neurons with renal input and renal pain, as a type of visceral pain. The renal pain was induced by ureteral occlusion or renal arterial occlusion, which in turn activated the renal mechanoreceptor or chemoreceptor. These cells had concomitant somatic input. In order to compare the effects of NRM stimulation on the renal pain with somatic pain, the somatic stimulation such as squeezing was conducted on the peripheral receptive field. The main results are summarized as follows: 1) After an electrical stimulation of NRM, spontaneous activities of dorsal horn neurons with renal input were reduced to 73.3 +/- 9.7% of the control value. 2) After an electrical stimulation of NRM, activities of dorsal horn neurons with renal input evoked by a brush, a type of non-noxious stimuli, did not change significantly. But the activities by a squeeze, a type of noxious stimuli, the activities were reduced to 63.2 +/- 7.2% of the control value. 3) After an electrical stimulation of NRM, activities of dorsal horn neurons with renal input evoked by occlusion of ureter or renal artery were reduced to 46.7 +/- 8.8% and 49.0 +/- 8.0% of the control value respectively. 4) The inhibitory effect of NRM on the dorsal horn neurons with renal input did not show any difference between renal A delta fiber and C fiber group. 5) By the electrical stimulation of NRM, the activities evoked by ureteral occlusion showed more reduction in the high threshold cell group than in the wide dynamic range cell group. These results suggest that activation of NRM can alleviate the renal pain as well as the somatic pain by modulating the dorsal horn neurons activities.

Afferent Pathways

Use of a 64 channel computerized cardiac mapping system in arrhythmia surgery.

A multipoint and computerized intraoperative mapping system has been known to be of value in improving the results of surgery for cardiac arrhythmia. It shows great potential as a new tool in the surgical intervention of the more common and lethal types of supraventricular tachyarrhythmias such as atrial flutter and atrial fibrillation. In addition, it also enhances the ability of the investigators to map and ablate the sometimes fleeting automatic atrial tachycardia. The authors developed a 64 channel computerized cardiac mapping system using a microcomputer (Macintosh IIx) and this has been used for basic research in cardiac electrophysiology as well as in arrhythmia surgery. In this system, bipolar electrograms are obtained from 64 different cardiac sites simultaneously at a sampling rate of 1 Ksample/sec and with a continuous and total data storage of up to 30 seconds. When the reference electrode is selected, delay time from the reference point is displayed on a two dimensional diagram of the heart. This system was used in one patient who underwent a surgical ablation of a ventricular tachycardia in whom we observed a ventricular activation sequence involving a variety of rhythms over several minutes. The system design permits easy expansion to a simultaneous sampling from 256 sites. This 64-channel mapping appeared to have the potential to be of great help in our understanding of cardiac arrhythmia as well as in its diagnosis and surgical treatment.

Arrhythmias, Cardiac

Characterization of the purinergic P2 receptors in PC12 cells. Evidence for a novel subtype.

The properties of the purinergic receptors in the PC12 cells were studied. The rank order of potency to increase [Ca2+]i was: adenosine 5'-O-(1-thiotriphosphate) > ATP > adenosine 5'-O-(3-thiotriphosphate) >>> 3'-O-(4-benzoyl-benzoyl)ATP. ADP, AMP, GTP, UTP, alpha, beta- and beta,gamma-methylene adenosine 5'-triphosphates, 5'-adenylylimido-diphosphate, and adenosine analogues were ineffective. Although tetrabasic ATP4- was the form responsible for activation of the P2 receptors, ATP4- did not cause cell membrane permeabilization. The binding of alpha-35S-ATP to the intact cells showed a divalent cation dependency and a binding profile similar to the rank order of potency to increase [Ca2+]i. Scatchard plots of the equilibrium saturation binding data were nonlinear, and dissociation kinetics of the radioligand were best described using two kinetic rates. Different kinetic rates were, however, obtained when dissociation was initiated by the addition of excess ATP or by an 80-fold dilution. The present study describes a purinergic P2 receptor on PC12 cells that does not fit the classification for the P2x, P2y, P2t, P2u, and P2z receptor subtypes.

Adenine Nucleotides

Nitric oxide reduces depolarization-induced calcium influx in PC12 cells by a cyclic GMP-mediated mechanism.

The present study was undertaken to determine whether nitric oxide (NO) alters voltage-dependent changes in intracellular calcium levels ([Ca2+]i) using PC12 cells as a neuronal model. The addition to PC12 cells of sodium nitroprusside (SNP), which spontaneously releases NO in aqueous solution, significantly inhibited the KCl-stimulated increase in [Ca2+]i. The inhibitory action of SNP was concentration-dependent and was mimicked by hydroxylamine which also generates NO. Both L-type (nifedipine sensitive) and N-type (omega-conotoxin sensitive) voltage-dependent Ca2+ channels are present in PC12 cells and may be affected by NO-generating agents. In contrast, SNP did not alter [Ca2+]i in response to purinergic receptor stimulation. Preincubation of PC12 cells with 8-bromo-cyclic GMP also inhibited the KCl-stimulated increase in [Ca2+]i. In addition, inclusion of the guanylyl cyclase inhibitor, LY83583, blocked the inhibitory action of SNP on the voltage-sensitive changes in [Ca2+]i. The results suggest that NO selectively inhibits voltage-dependent calcium influx in neuronal cells through a cyclic GMP-dependent mechanism.

Action Potentials

In murine AIDS, B cells are early targets of defective virus and are required for efficient infection and expression of defective virus in T cells and macrophages.

Previous studies showed that B cells and CD4+ T cells are required for induction of a murine retrovirus-induced immunodeficiency syndrome, murine AIDS. Using B6 mice deficient in mature B cells as a result of a knockout of the transmembrane exon of the immunoglobulin M gene, we found that spleen and other tissues from murine AIDS virus-infected mice did not express the defective virus (BM5def) required for induction of disease, even though helper viruses were readily detectable and BM5def proviral DNA was present. This indicates that the B-lineage cells are the primary targets for infection and expression of the defective virus and that in the absence of mature B cells, there is inefficient infection of T cells and macrophages.

Actins

A gradient-layer calorimeter for measurement of energy expenditure of infants.

We have developed and validated a gradient-layer calorimeter for direct measurement of energy expenditure of preterm infants. Infant calorimeters must be operated and tested differently from adult calorimeters, because the calorimeter must be warmed during operation to limit heat loss from the infant, the calorimeter wall temperature (which is selected on the basis of the infant's maturity) must be precisely controlled, and energy expenditure (heat output) is typically < 10 W. We calibrated our calorimeter by varying the heat produced by a dry source (manikin or light bulb) with airflow (n = 42) and without airflow (n = 8) at various water jacket temperatures (n = 7) and by a wet source (combustion of ethyl alcohol) with airflow (n = 9). With no air moving, qc = 0.740 Vc + 0.029 Twj-0.697, where qc (W) is the estimated output of the heat source measured by the calorimeter, Vc (mV) is the gradient-layer voltage of the calorimeter, and Twj (degree C) is the temperature of the water jacket surrounding the walls of the device. From this equation and enthalpy calculations, the slope and intercept of the regression line relating the estimated heat production to the actual heat produced from alcohol combustion are 1.029 +/- 0.046 and -0.549 +/- 0.484 (SE), respectively. The slope is not significantly different from unity, and the intercept is not significantly different from zero. Thus we can accurately estimate the energy expenditure of preterm infants from the equations describing our calorimeter, and we can accurately resolve the total heat output into a dry (nonevaporative) component and a wet (evaporative) component.

Calibration

The roles of revascularization and resorption on endurance of craniofacial onlay bone grafts in the rabbit.

A total of 32 New Zealand white rabbits underwent subperiosteal implantation of fresh autogenous unicortical calvarial and iliac crest grafts on their snouts with microscrew rigid fixation. After 3 and 10 days, vascularity was assessed by latex casting, and osteoclastic activity was determined by histochemical staining for tartrate-resistant acid phosphatase. After 70 days, volumetric analysis and tartrate-resistant acid phosphatase staining were performed on six animals. The calvarial grafts demonstrated greater volume maintenance than the iliac bone (72 percent versus 32 percent, p < 0.025). There were significantly greater osteoclastic activity and revascularization in the cancellous portion of calvarial and iliac crest bone grafts by the 10th day of onlay grafting. Minimal activities were present at the cortical bone. Because calvarial grafts contain more cortical bone, its superior volume maintenance can be understood by the architectural influence on revascularization and resorption.

Animals

Chronic ethanol exposure inhibits ATP-stimulated but not KCl-stimulated dopamine release in PC 12 cells.

The functional significance of the ethanol-induced alterations in intracellular concentration of free calcium ([Ca++]i) was determined in PC 12 cells by measuring agonist-stimulated dopamine (DA) release after ethanol exposure. ATP and KCl produced a concentration-dependent release of DA, which was linearly related to the net increase in [Ca++]i, but different relationships were observed with ATP and KCl. Acute addition of 150 mM ethanol inhibited KCl-stimulated release of DA, but did not alter the response to ATP. In contrast, a 4-day exposure to 150 mM ethanol led to a reduction in ATP-evoked DA release without altering the response to KCl. Furthermore, a 7-day treatment with 25 mM ethanol also decreased the response to ATP. Acute and chronic ethanol exposures, however, did not alter the relationships between DA release and the increase in [Ca++]i observed with ATP and KCl. The data indicate that acute and chronic ethanol treatments have differential effects on the responses to extracellular ATP and KCl and alter DA release primarily by altering the calcium influx stimulated by agonists.

Adenosine Triphosphate

Chronic ethanol exposure potentiates muscarinic receptor and alpha 2-adrenoceptor-mediated inhibition of cAMP accumulation in PC 12 cells.

The effects of ethanol on receptor-mediated inhibition of cAMP production were investigated in PC 12 cells. The in vitro addition of ethanol enhanced N-ethylcarboxyadenosine (NECA)-stimulated cAMP production without altering the inhibitory action of carbachol or epinephrine. A 4 day exposure of PC 12 cells to ethanol decreased the stimulation of cAMP production by NECA, but increased the inhibition of NECA-stimulated cAMP production by carbachol and epinephrine.

Adenosine

Differential effects of chronic ethanol exposure on ATP- and bradykinin-induced increases in intracellular calcium levels in PC-12 cells.

The present study investigated the regulation of intracellular calcium levels ([Ca2+]i) by ethanol, ATP, and bradykinin (BK) in PC-12 cells. Acute addition of 150 mM ethanol increased [Ca2+]i but did not alter ATP- and BK-induced increases in [Ca2+]i. After a 4-day exposure to 150 mM ethanol, the maximal response to ATP was decreased 39.7 +/- 8.12% (p < 0.01), whereas that to BK was increased 43.8 +/- 6.81% (p < 0.01). There was no change in the EC50 values for either ATP or BK after chronic ethanol exposure. Addition of excess ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) to remove extracellular free calcium prevented the ATP-induced increase in [Ca2+]i. In contrast, BK produced an increase in [Ca2+]i in the presence of excess EGTA, suggesting that BK releases calcium from internal stores. Consistent with this suggestion, chronic ethanol exposure enhanced BK-induced phosphoinositide hydrolysis. ATP, however, did not increase phosphoinositide hydrolysis. Pretreatment with 10 microM nifedipine, which blocked depolarization-evoked increases in [Ca2+]i, reduced ATP- and BK-induced increases in [Ca2+]i but did not alter the response to chronic ethanol exposure. Although acute addition of ethanol reduced KCl-stimulated increases in [Ca2+]i and 45Ca2+ uptake, chronic ethanol exposure did not alter the depolarization-induced increase in [Ca2+]i or 45Ca2+ uptake. The present study demonstrates that chronic ethanol exposure inhibits calcium influx through voltage-independent cationic channels associated with purinergic receptors and enhances BK-stimulated phosphoinositide hydrolysis, with a subsequent release of calcium from internal stores.

Adenosine Triphosphate

A region of heterogeneity adjacent to the 5s ribosomal RNA gene of cereal rusts.

Total genomic DNA was isolated from three cereal stem rusts, Puccinia graminis f. sp. tritici, f. sp. secalis, f. sp. avenae, and two cereal leaf rusts, P. recondita f. sp. tritici and P. coronata f. sp. avenae, and analyzed for the presence of heterogeneity in the intergenic region of the ribosomal DNA repeat unit. A 1 kb region of the repeat unit between the 26s and the 5s rRNA genes (IGR-1) was amplified by PCR and was found to be heterogeneous within each isolate and variable in size between races and species. The PCR results were confirmed by Southern blot analysis of native DNA. In an isolate of race C36(48), heterogeneity appeared to be due to variable numbers of 0.1 kb subrepeats in IGR-1. Nine wheat stem rust strains representing nine different races produced a unique pattern of heterogeneity while two different isolates of one race were identical, as were five of another. This may provide a rapid method for race identification in wheat stem rust. Heterogeneity and polymorphism in rye stem rust, oat stem rust, wheat leaf rust, and oat crown rust, was less pronounced than in wheat stem rust. In the course of this work, the 5s rRNA gene was located and its position and orientation within the ribosomal repeat unit was established.

Base Sequence

Immunoneutralization of gonadotropin-releasing hormone and subsequent treatment with testosterone Silastic implants in rats: an approach toward developing a male contraceptive.

STUDY OBJECTIVE: To determine the extent to which increasing doses of exogenous testosterone (T) administered via Silastic implants can restore spermatogenesis and fertility to rats made azoospermic by active immunization against gonadotropin-releasing hormone (GnRH). DESIGN: Male rats were made azoospermic by active immunization against GnRH. Increasing doses of exogenously administered T (via Silastic implants) were administered for 8 weeks, and testicular sperm concentration and ability to impregnate female rats were evaluated. SETTING: Reproductive Endocrinology Laboratory, Department of Obstetrics and Gynecology, University of Colorado Health Sciences Center, Denver, Colorado. ANIMALS: Sexually mature male Sprague Dawley rats (SASCO, Omaha, NE). RESULTS: Suppression of gonadotropins and azoospermia was achieved by actively immunizing rats against GnRH. Testosterone was capable of restoring quantitatively complete spermatogenesis and fertility in GnRH-immunized azoospermic rats. This relationship was dose-dependent, as evidenced by the partial restoration of spermatogenesis and fertility observed in animals replaced with smaller T Silastic implants. CONCLUSION: Gonadotropin-releasing hormone immunization and T-filled Silastic implants may provide a model to study isolated gonadotropin deficiency and for the development of a reversible male contraceptive.

Animals

Soft-tissue alterations associated with acute, extended open reduction and internal fixation or orbital fractures.

Soft-tissue alterations associated with radical degloving of the overlying soft tissues during extended open reduction and rigid internal fixation of facial fractures involving 51 orbits in 36 patients were studied. In all patients, the blepharoplasty skin muscle flap incision was employed in conjunction with, as necessary, a gingivobuccal sulcus and coronary incisions. Patients were evaluated between 6 and 20 months after surgery. Physical examination and standardized photographs were used for assessment. Ectropion developed in 2 lids (4%), and 10 lids (20%) had increased scleral show. Thirteen of the 51 lids (25%) revealed lateral canthal displacement; all 13 lids underwent canthal stripping. Cheek pad displacement developed in 8 patients (22%), all of whom had complete maxillary degloving without soft-tissue resuspension. No patient had frontal nerve palsy. Depression in the temporal area was noted in all patients in whom the temporalis was mobilized. Remote incisions and soft-tissue degloving used for extended open reduction and internal fixation are associated with morbidity that can be minimized by meticulous technique and soft-tissue repositioning at closure.

Adolescent