Biomedical subjects

D J Lim

Publications and source records attributed to D J Lim.

At least 37 records · Page 2Linked to original sources

PubMed1998

Cell and molecular basis of hearing.

The mammalian auditory organ is a specialized sensory epithelium capable of detecting subnanometer movements produced by sound and transducing them into electrical signals. It is a dual system consisting of two types of sensory cells: the inner hair cells, which provide afferent input to the central nervous system, and the outer hair cells, which provide frequency resolution and signal amplification. The critical element in mechano-reception is the hair bundle, a cluster of stereocilia located in the apical end of the sensory cells. Mechanical stimulation causes deflection of ciliary bundles that leads to the opening or closing of transduction channels located in the apical part of the plasma membrane of the stereocilia. The current concept of auditory function requires an active process of signal amplification within the cochlea. It is generally believed that outer hair cells, functioning as both sensor and motor elements, are responsible for this amplification process. The motor function consists of changes in cell length produced by the concerted action of a large number of independent molecular motors distributed along the length of the outer hair cell lateral plasma membrane. Although experimental evidence suggests its association with conformational changes in transmembrane proteins, the exact nature of the outer hair cell force generation mechanism on a molecular level is still unknown.

Animals↗

PubMed1997

Detoxified lipooligosaccharide from nontypeable Haemophilus influenzae conjugated to proteins confers protection against otitis media in chinchillas.

Detoxified-lipooligosaccharide (dLOS)-protein conjugates from nontypeable Haemophilus influenzae (NTHi) elicited a significant rise of anti-LOS antibodies with bactericidal activity in rabbits (X.-X. Gu, C.-M. Tsai, T. Ueyama, S. J. Barenkamp, J. B. Robbins, and D. J. Lim, Infect. Immun. 64:4047-4053, 1996). In this study, we evaluated whether vaccination with the conjugates would protect against NTHi otitis media in chinchillas. Fifty-eight chinchillas received three subcutaneous or intramuscular injections of dLOS-conjugated tetanus toxoid, dLOS-conjugated high-molecular-weight proteins from NTHi, or saline (control) in Freund's adjuvant and then were challenged by intrabullar inoculation with 140 CFU of NTHi. All vaccinated animals responded with elevated serum titers of anti-LOS antibody, and 49% (19 of 39) demonstrated bactericidal activity against the homologous strain. Otitis media with culture-positive NTHi effusions developed in all 19 controls and 56% (22 of 39) of the vaccinated animals during a period of 21 days (P < 0.001). Bacterial counts of the middle ear effusions were lower in the vaccine groups than in the controls (P < 0.01). The incidences of infection in the unchallenged ear or inner ear were 26 or 28% in the vaccine groups and 53 or 58% in the controls (P < 0.05). The signs of infection observed by otoscopy were less severe in the vaccine groups than in the controls. There was no significant difference between the two vaccine groups. These data indicate that active immunization with LOS-based conjugates reduces the incidence of NTHi-induced otitis media.

Animals↗

PubMed1996

Tectorial membrane-organ of Corti relationship during cochlear development.

The development of stereociliary attachment to the tectorial membrane was investigated in the mouse cochlea using transmission and scanning electron microscopy. At the 18th gestational day, only the major tectorial membrane can be identified covering the greater epithelial ridge and the inner hair cells in all turns. At the 19th gestational day, the minor tectorial membrane was first seen in the basal turn, over the outer hair cells. During early stages of development, the stereocilia of hair cells were surrounded by a loose fibrillar material underneath the tectorial membrane. After the 10th postnatal day, the outer hair cells' stereocilia were attached to Kimura's (or Hardesty's) membrane, while inner hair cells' stereociliary bundles were attached to the undersurface of the tectorial membrane near the Hensen's stripe. Between the 10th and the 14th postnatal days, the space between the inner hair cells and the first row of outer hair cells widened by virtue of the growth of the heads of pillar cells, and the inner hair cells' stereocilia were displaced towards the Hensen's stripe. After the 14th postnatal day, the inner hair cells' stereociliary bundles detached from the tectorial membrane, while the outer hair cells' stereocilia remained attached to it. The tip-link system, which connects the tips of the stereocilia to the next tallest stereocilia, is present at birth in the outer hair cells. The marginal pillar, that anchored the tectorial membrane to the underlying organ of Corti during development, first appeared on the 6th postnatal day and disappeared on the 14th-15th postnatal day. The present data together with other reports support the idea that although some structures, such as hair cells' stereocilia and innervation, are already formed early during development, the cochlear microarchitecture is not fully developed morphologically and ready to function normally until the end of the second postnatal week in the mouse.

Animals↗

PubMed1996

Crossed ectopia of ovotestis in a case of true hermaphroditism.

True hermaphroditism is a rare form of intersex disorder. The authors report a case of true hermaphroditism with crossed ectopia of an ovotestis from the left to the right scrotum. The karyotype of the patient was 46,XX, without mosaicism. The majority of the ovotestis was comprised of testicular tissue. In other cases of human true hermaphroditism, descent of a pure ovary has not been noted to occur, despite the presence of the contralateral testis. Additionally, in congenital adrenal hyperplasia occurring in genotypic female subjects, pure ovaries do not descend into the scrotum despite the high level of androgens. Taken together, we believe that the demonstrated descent of mostly testicular ovotestes supports the idea that the testis produces a substance other than androgen that is important in guiding its descent.

Choristoma↗

PubMed1996

Treatment of pediatric urolithiasis between 1984 and 1994.

PURPOSE: We report our experience with the management of pediatric urolithiasis during a 10-year period. Our aim was to assess the impact of new technology in the treatment of pediatric urolithiasis. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients up to age 18 years in whom urolithiasis was treated from 1984 to 1994. In 37 cases 24-hour urine collections were available for metabolic evaluation. RESULTS: A total of 100 pediatric patients was treated for urolithiasis. Mean followup was 36 months. A total of 79 patients underwent 115 procedures for symptomatic urolithiasis and 21 were treated nonoperatively. In 42 patients structural anomalies of the urinary tract required additional management. Metabolic abnormalities in 48 patients included hypercalciuria in 19, defined as greater than 4 mg./kg./24 hours calcium by 24-hour urine collection. Only 24 of the 100 patients had no identifiable predisposing factors. Procedures included shock wave lithotripsy in 42 cases, basket extraction with or without ureteroscopy in 20, percutaneous nephrostolithotomy in 11 and litholapaxy in 12. Open surgery included cystolithotomy in 10 cases and other forms of open lithotomy in 15. Thus, open surgical removal was necessary in 1 of 5 cases. CONCLUSIONS: Compared to the traditional mode of stone treatment, fewer patients required open surgery. Our results indicate that a comprehensive approach to the care of pediatric patients with urolithiasis requires attention to metabolic and structural abnormalities.

Adolescent↗

PubMed1996

Management of the failed pyeloplasty.

PURPOSE: We present our experience with repeat surgery for persistent ureteropelvic junction obstruction. MATERIALS AND METHODS: We retrospectively reviewed the records of patients who underwent pyeloplasty for ureteropelvic junction obstruction between 1984 and 1994, focusing on those who underwent repeat surgery for persistent ureteropelvic junction obstruction after initial pyeloplasty. RESULTS: During the 10-year period 127 pyeloplasties were done by a single surgeon (R. D. W.). Three cases of persistent ureteropelvic junction obstruction occurred in this primary pyeloplasty series (success rate 97.6%). During the same period 9 other patients were referred to us from elsewhere for persistent ureteropelvic junction obstruction after initial pyeloplasty (total 12 patients). Ten patients underwent repeat pyeloplasty with a postoperative stent in place. Two patients needed nephrectomy at the initial repeat procedure and 1 of the 10 repeat pyeloplasty patients ultimately underwent nephrectomy. Six patients who had recurrent ureteropelvic junction obstruction were younger than 6 months at the time of the original pyeloplasty. Excessive urinary drainage was noted in 2 of our 3 cases of failed pyeloplasty. Thus, in 9 patients satisfactory resolution of obstruction was achieved by repeat pyeloplasty (salvage rate 75%). CONCLUSIONS: Persistent ureteropelvic junction obstruction is an uncommon complication after pyeloplasty. Infants who undergo pyeloplasty may be more prone to persistent obstruction after pyeloplasty. Prolonged urinary drainage seems to be a harbinger of persistent ureteropelvic junction obstruction. Careful repeat pyeloplasty with attention to preservation of the blood supply and meticulous watertight anastomosis led to satisfactory resolution of ureteropelvic junction obstruction in 75% of the cases.

Adolescent↗

PubMed1996

Synthesis, characterization, and immunologic properties of detoxified lipooligosaccharide from nontypeable Haemophilus influenzae conjugated to proteins.

Nontypeable Haemophilus influenzae (NTHi) is an important cause of otitis media in children and of pneumonitis in adults with depressed resistance. Lipooligosaccharide (LOS) is a major surface antigen of NTHi and elicits bactericidal and opsonic antibodies. We prepared detoxified LOS (dLOS) protein conjugates from NTHi for use as experimental vaccines. LOS from NTHi 9274 was treated with anhydrous hydrazine and had its toxicity reduced to clinically acceptable levels. dLOS was bound to tetanus toxoid (TT) or high- molecular-weight proteins (HMPs) from NTHi through a linker of adipic acid dihydrazide to form dLOS-TT or dLOS-HMP. The molar ratio of the dLOS to protein carriers ranged from 26:1 to 50:1. The antigenicity of the conjugates was similar to that of the LOS alone as determined by double immunodiffusion. Subcutaneous or intramuscular injection of the conjugates elicited a 28- to 486-fold rise in the level of immunoglobulin G antibodies in mice to the homologous LOS after two or three injections and a 169- to 243-fold rise in the level of immunoglobulin G antibodies in rabbits after two injections. The immunogenicity of the conjugates in mice and rabbits was enhanced by formulation with monophosphoryl lipid A plus trehalose dimycolate. In rabbits, conjugate-induced LOS antibodies induced complement-mediated bactericidal activity against the homologous strain 9274 and prototype strain 3189. These results indicate that a detoxified LOS-protein conjugate is a candidate vaccine for otitis media and pneumonitis caused by NTHi.

Animals↗

PubMed1996

Common sheath reimplantation yields excellent results in the treatment of vesicoureteral reflux in duplicated collecting systems.

PURPOSE: We evaluated our 10-year experience with the surgical treatment of vesicoureteral reflux in uncomplicated duplicated collecting systems. MATERIALS AND METHODS: Between 1984 and 1994, 54 refluxing renal units (8 bilateral) in 37 female and 9 male patients required surgery. Patient age ranged from 7 months to 17 years (average 4.9 at surgery). Postoperative followup (average 14.2 months) included voiding cystourethrography and renal sonography or excretory urography. RESULTS: Common sheath ureteral reimplantation via an intravesical approach was performed in 48 of the 54 refluxing renal units. Of the remaining 6 renal units detrussorrhaphy was performed in 4, and ureteroureterostomy combined with ureteral reimplantation and partial lower pole nephrectomy were done in 1 each. Two treated renal units had persistent postoperative vesicoureteral reflux, which resolved after subureteral polytetrafluoroethylene (Teflon) injection. No renal had postoperative hydronephrosis. Contralateral reflux was identified in 1 patient who underwent unilateral reimplantation. Our overall success rate was 96% for the surgical correction of vesicoureteral reflux in uncomplicated duplicated collecting systems. Common sheath reimplantation had a 98% success rate. CONCLUSIONS: Although a duplicated collecting system increases the risk for surgical treatment, the presence of a duplication anomaly does not adversely affect surgical outcome. Modifications of procedures commonly performed in the surgical treatment of single system reflux to accommodate common sheath reimplantation have excellent surgical results with minimal morbidity.

Adolescent↗

PubMed1995

Amiloride-sensitive Na+ channel-like immunoreactivity in the luminal membrane of some non-sensory epithelia of the inner ear.

Some non-sensory epithelia of the inner ear were examined for the localization of immunoreactivity to polyclonal antibodies raised against amiloride-sensitive Na+ channels from the bovine kidney. The pre-embedding immunogold technique was used for this purpose. Labelings were found on the membrane of the endolymphatic surface of strial marginal cells, epithelial cells of spiral prominence and Reissner's membrane, and ampullar dark cells. In contrast, no labeling was found on the luminal membrane of mesothelial cells of Reissner's membrane, the cells lining the supra-strial perilymphatic space, transitional cells and ampullar ceiling cells. Since the antibodies used may also label non-selective cation channels and non-functional sodium channel precursors as suggested by others, it was not possible to determine the labelings are solely due to amiloride-sensitive Na+ channels. However, the observed result was consistent with the previous studies that amiloride blocks ion transport in strial marginal cells and the semicircular canal. It is therefore likely that the observed labeling includes amiloride-sensitive Na+ channels. These labeled ion channels in a variety of epithelial cells lining the endolymphatic space could be important in the inner ear fluid regulation.

Amiloride↗

PubMed1995

Quantitation and biological properties of released and cell-bound lipooligosaccharides from nontypeable Haemophilus influenzae.

Nontypeable Haemophilus influenzae (NTHi) is a major pathogen causing otitis media in children. NTHi releases lipooligosaccharide (LOS) as outer membrane fragments during its growth. The release of LOS may play an important role in the pathogenicity of otitis media caused by this organism. The amounts of LOS in bacterial cells and growth media for five NTHi strains were determined by quantitative silver staining after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These strains were estimated to have 1.6 x 10(6) to 4.8 x 10(6) LOS molecules per bacterium. During a 3-day growth period, these NTHi strains released variable but significant amounts of LOS into the growth medium. Cells started to release detectable amounts of LOS into the medium at 2 to 5 h and continued to do so for up to 48 or 72 h. The concentrations of LOS in the culture supernatants released by these five strains were 10 to 55 micrograms/ml at 24 h and 40 to 100 micrograms/ml at 72 h, which was 34 to 189% of the cell-bound LOS concentration. The biological properties of released and cell-bound LOSs from two representative strains were compared. Released LOS showed an approximately 10-fold increase in inducing human monocytes to produce tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6, a 13- to 28-fold increase in mouse lethal toxicity, and a 16- to 37-fold increase in the clotting of Limulus amebocyte lysate. These results suggested that released LOS or its inflammatory mediators play a more important role than the LOS in bacteria in the pathogenicity of otitis media caused by this organism.

Animals↗

PubMed1995

Relationship between tissue plasminogen activator, plasminogen activator inhibitor and CT image in chronic subdural hematoma.

The present study was performed to investigate the relationship between the concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) and the CT images in 23 cases of chronic subdural hematomas (SDHs). The concentrations of t-PA and PAI-1 were quantified by enzyme-linked immunosorbent assay (ELISA). Chronic SDHs were divided into five groups according to their appearance on computed tomography: high-density (n = 4), isodensity (n = 8), low-density (n = 5), mixed-density (n = 3), layering (n = 3) types. The volume of hematoma was measured with an image analyzing software program. The concentrations of t-PA were higher in layering (41.2 +/- 0.3 ng/ml, mean +/- standard error of the mean) and high-density (40.0 +/- 1.1 ng/ml) types compared to those of low-density (23.3 +/- 4.1 ng/ml) and iso-density (25.1 +/- 3.7 ng/ml) types. The concentrations of PAI-1 were lower in layering (95.9 +/- 1.0 ng/ml) and high-density (103.4 +/- 34.5 ng/ml) types compared to that of low-density (192.5 +/- 2.6 ng/ml) type. So the ratio between t-PA and PAI-1 (t-PA/PAI) was greater in layering and high-density types. The volume of hematoma was larger in mixed-density and layering types but statistically insignificant. These results presumably suggest that the ratio between t-PA and PAI concentration may contribute to the pathogenesis of the chronic SDH.

Adult↗

PubMed1995

Rectus fascial wrap: early results of a modification of the rectus fascial sling.

We describe an operation that increases bladder neck resistance in patients with urinary incontinence. It is a modification of the rectus fascial sling that was designed as an adjunct to augmentation cystoplasty and is used in association with clean intermittent catheterization. The operation is performed by circumferentially wrapping a rectus fascial defatted free graft around the bladder neck and suturing it to appose the bladder neck. The procedure was done in 17 patients, including 10 with myelodysplasia, 3 with sacral lipoma, 3 with bladder exstrophy and 1 with nonneurogenic neurogenic bladder. Leak point pressure improved in patients in whom it was measured preoperatively and postoperatively. Complications developed in 5 patients, including difficulty with catheterization in 2, ventral hernia at the graft harvest site in 1, bladder calculus in 1 and detrusor hyperreflexia in 1. Early results with the bladder fascial wrap indicate that it has the ability to improve continence in patients with a dysfunctional bladder neck who have undergone augmentation.

Adolescent↗

PubMed1995

Structure and function of the tympanic membrane: a review.

Advances made in the last three decades of research on morphological, cell biological, and immunobiological aspects of the tympanic membrane of laboratory animals and humans are reviewed. The tympanic membrane is composed of the pars flaccida and pars tensa with considerable variations in their size and thickness. Both pars flaccida and pars tensa consist of an epidermal layer, a lamina propria, and a mucosal epithelial layer. The fibrils of the fibrous layer contain a large amount of type II and type III collagen, and a small amount of type I collagen. It has been suggested that such an unusual collagen composition is the underlying reason for the unique physical feature of the pars tensa of the tympanic membrane. A large number of mast cells are found in the Shrapnell's membrane and these cells are suggested to be responsible for the production of middle ear effusion. The cellular basis for the epidermal migration and the role of epidermal and fibroblast growth factors in epidermal cell proliferation and in wound healing are also reviewed. Future research directions on tympanic membrane biology and pathobiology are discussed.

Humans↗

PubMed1995

Correction of retractile concealed penis.

Several different mechanisms may account for the concealed appearance of the penis. A particular type of concealed penis is the retractile penis, due to dysgenetic fibrous bands tethering the penis to the prepubic subcutaneous tissue. The retractile nature of the concealment can be confirmed by flexion of the hips. A simple technique for surgical correction of the retractile penis is described. While there are many different methods to correct a concealed penis, proper selection of the technique based on understanding of the pathophysiology is critical to a successful outcome.

Child↗

PubMed1994

Amiloride-sensitive channels in marginal cells in the stria vascularis of the guinea pig cochlea.

We examined marginal cells in stria vascularis for the presence of amiloride-sensitive Na+ channels, a possible pathway for maintaining a low Na+ concentration in the endolymph. Whole-cell voltage-clamp experiment shows that amiloride at 1 microM concentration reversibly reduces inward current more than outward current. Immunogold-labeling method shows that the luminal and lateral membrane have antigenic sites for these antibodies. These observations indicate the presence of amiloride-sensitive channels in the marginal cell. If amiloride-sensitive channels in the luminal membrane are highly selective to Na+, they could be an efficient pathway for Na+ uptake from the endolymph. In the basolateral membrane, amiloride-sensitive Na+ channels may make a relatively small contribution to the unusual resting potential.

Amiloride↗

PubMed1994

Effect of intranasal inoculation of Streptococcus pneumoniae on the structure of the surface carbohydrates of the chinchilla eustachian tube and middle ear mucosa.

The changes in the cell surface carbohydrates of the eustachian tube (ET) and middle ear subsequent to the intranasal (i.n.) inoculation of Streptococcus pneumoniae (Spn) type 6A were studied in the chinchilla model of otitis media (OM) using a lectin histochemical technique with six different lectins (SNA, WGA, Succ WGA, BSL II, PNA, ECL). The labeling pattern revealed not only the removal of the terminal sialic acid, but also exposure of N-acetylglucosamine (GlcNAc), a component of the trisaccharide receptor for Spn previously identified on human pharyngeal cells. The removal of sialic acid residues progressed from the nasopharyngeal to the tympanic orifice and was most pronounced in those animals from which Spn could be isolated from the middle ear. Our data indicate an alteration of the normal lectin labeling pattern and exposure of GlcNAc restricted mainly to the roof and neck portion, along the course of the eustachian tube. Exposure of part or all of a Spn adherence receptor structure by the pneumococcal enzymes, may facilitate colonization, invasion of the middle ear, and induction of OM.

Animals↗

PubMed1994

Peptidoglycan isolated from nontypeable Haemophilus influenzae induces experimental otitis media in the chinchilla.

Bacterial cell wall components induce a number of biologic effects and promote inflammatory changes in a variety of hosts. Peptidoglycan isolated from Streptococcus pneumoniae can induce inflammation in the middle ear; however, an analogous role for peptidoglycan derived from gram-negative otitis media pathogens has not been described. Peptidoglycan isolated from nontypeable Haemophilus influenzae (NTHi), a major cause of otitis media, was evaluated in a chinchilla model. The direct injection of the middle ear with 3-300 micrograms of peptidoglycan resulted in tympanic membrane inflammation, abnormal pressure in the middle ear, leukocytosis, and histopathologic changes in the middle ear mucosa that included marked edema, osteoneogenesis, focal hemorrhage, and a mononuclear infiltration into the subepithelial space. These data indicate that NTHi peptidoglycan induced inflammation and histopathologic changes in the tympanic membrane and middle ear mucosal epithelium and may contribute to the pathogenesis of otitis media.

Animals↗

PubMed1994

Moraxella (Branhamella) catarrhalis-induced experimental otitis media in the chinchilla.

Otitis media was introduced in chinchillas by direct transbullar inoculation with either viable or formalin-inactivated Moraxella (Branhamella) catarrhalis. Both groups of animals developed middle ear fluids (MEF) and severe inflammatory changes in the tubotympanum. Pure cultures of M. catarrhalis were recovered for up to 5 days after inoculation from those animals inoculated with viable bacteria. Significantly elevated anti-M. catarrhalis antibody titers were detected in post-inoculation sera and in MEF or bullar lavages, and an increased number of IgG-bearing cells was also observed in the tubotympanum of these animals. Control chinchillas inoculated with pyrogen-free sterile saline failed to show any signs of otitis media. Our data indicate that viable M. catarrhalis induce acute otitis media in the chinchilla but that the bacteria are rapidly eliminated from the middle ear, precluding its usefulness as a model to study acute otitis media. Moreover, the same concentration of nonviable organisms also induces severe inflammatory changes in the middle ear. These data indicate that the chinchilla may be a useful model for studying the role of nonviable M. catarrhalis or its cell wall components on the induction and persistence of inflammation in the middle ear.

Animals↗