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Biomedical subjects

K Lew

Publications and source records attributed to K Lew.

At least 19 recordsLinked to original sources

Meatoplasty keloid: a rare lesion treated with an unusual surgical approach.

Keloid scarring is a benign hyperproliferation of fibrous tissue occurring at a wound healing site. Keloid formation related to the ear is generally the result of ear-piercing, mainly causing cosmetic disfigurement. We present an unusual case of keloid formation at a previous meatoplasty incision scar in a 10-year-old Caucasian with a modified radical mastoid cavity. This lesion prevented the cavity from self-cleaning and obstructed microscopic evaluation of the cavity. Treatment was successfully performed by surgical excision, with closure of the defect using supra-keloid skin flaps, followed by serial steroid injection therapy.

Child↗

Failure to obtain adequate anaesthesia associated with a bifid mandibular canal: a case report.

The inferior alveolar nerve (IAN) block is the most common method for obtaining mandibular anaesthesia in dental practice but it is estimated to have a success rate of only 80 to 85 per cent. Causes of failure include problems with operator technique and anatomical variation between individuals. This case report involves a patient who received IAN blocks on two separate occasions that resulted in only partial anaesthesia of the ipsilateral side of the mandible. Radiographic assessment disclosed the presence of bifid mandibular canals that were present bilaterally and that may have affected the outcomes of the local anaesthetic procedures. Previous studies of bifid mandibular canals are reviewed and suggestions provided that should enable clinicians to differentially diagnose, and then manage, cases where IAN blocks result in inadequate mandibular anaesthesia.

Anesthesia, Dental↗

Dietary practices of adolescents in Singapore and Malaysia.

INTRODUCTION: This study sets out to investigate any differences in dietary practices between adolescents in Singapore and Malaysia. METHODS: An adolescent dietary practices survey was conducted in Singapore and Malaysia involving 200 adolescents (100 from each country) aged 11 to 21 years in order to have a better understanding of the adolescents' dietary practices. Dietary practices were assessed by a self-administered dietary practices questionnaire (DPQ). RESULTS: The major differences identified between adolescents' dietary practices in Singapore and Malaysia are related to alcohol consumption and venue for taking of lunch. More Malaysian adolescents have their lunch prepared at home (32.9 percent), compared with 7.2 percent of Singaporean adolescents. More adolescents in Malaysia drink alcohol (49.4 percent), compared with only 21.7 percent of Singaporean adolescents. CONCLUSION: From the dietary practices survey of adolescents from Singapore and Malaysia, it may be concluded that while general dietary practices are similar, the major differences identified were significantly (p-value is less than 0.05) higher alcohol consumption by Malaysian adolescents and significantly (p-value is less than 0.05) more Malaysians took their lunch at home compared with Singaporeans. The reasons for the differences are discussed in the paper.

Adolescent↗

Quantitative distinctions of active site molecular recognition by P-glycoprotein and cytochrome P450 3A4.

The bulk of characterized xenobiotic defense and disposition is conferred by the abundant enzymes cytochrome P450 3A4 and P-glycoprotein. Although expressed in many tissues, these enzymes are most abundant in the liver and intestine and seem to share most substrates and inhibitors, with the apparent synergy between these two promiscuous enzymes asserted because of their extensive overlap of substrates and shared tissue location. Since the broad-spectrum tolerance to lipophilic compounds of various sizes naturally results in a similar pattern of substrate/inhibitor recognition, the cause or mechanism of many drug/drug and drug/herb interactions can be difficult to determine. These two seemingly indiscriminate enzymes, however, do not share some unique inhibitor selectivity. Particularly, we show various potent CYP3A4 inhibitors that do not affect P-gp active transport function. Remarkably, we have also identified several compounds-valinomycin, norverapamil, reserpine, nobiletin, emetine, gallopamil, fluphenazine-that uniquely inhibit P-gp function with affinities comparable to benchmark P-gp inhibitors despite a lack of effect on CYP3A4 function at physiologically relevant concentrations. Indeed, valinomycin inhibits P-gp with an IC(50) similar to cyclosporin A yet apparently does not affect CYP3A4 function, and emetine and nobiletin are also specific for interaction with P-gp. Additionally, norverapamil and reserpine have, respectively, a 60- and 40-fold preference for inhibition of P-gp over CYP3A4. Some striking structural analogies among these compounds are discussed. These distinguishing qualities of substrate recognition between CYP3A4 and P-gp should reveal nuances of active-site architecture unique to each and could serve as tools to probe for the specific discernment of P-gp-mediated drug/drug or drug/herb interactions. Learning more about binding distinctions and quantitative activity relationships of substrate/inhibitor interactions with these two enzymes and the differences between them may indicate how they recognize such a wide variety of molecules as substrates (and/or inhibitors). Moreover, identification of specific inhibitors will allow the determination of which enzyme is responsible for drug interactions and/or the extent of contribution in a multiple exposure situation.

3T3 Cells↗

Refractory heterotopic ossification with complications.

BACKGROUND: Heterotopic ossification (HO) following spinal cord injury can lead to various complications, including venous thrombosis, autonomic dysreflexia, and pressure ulcers. We report refractory, complicated HO in a 19-year-old man with C8 incomplete tetraplegia. He first presented at 9 weeks postinjury with fever and swelling of his right leg. Ultrasound indicated a deep venous thrombosis (DVT). Persistent symptoms prompted triple-phase bone scan and magnetic resonance imaging (MRI), which revealed HO compressing the right external iliac vein and no evidence of DVT. The HO was complicated by hypercoagulability. CLINICAL COURSE: The HO was refractory to oral indomethacin and etidronate; therefore, intravenous etidronate was instituted, resulting in only a transient decrease in alkaline phosphatase. Local irradiation of the right hip did not decrease the activity of HO. The patient was discharged on oral etidronate, indomethacin, and warfarin. This complicated case raises issues regarding early diagnosis and aggressive treatment of HO, as well as treatment of associated hypercoagulability.

Constriction, Pathologic↗

Epithelial mucin-1 (MUC1) expression and MA5 anti-MUC1 monoclonal antibody targeting in multiple myeloma.

Multiple myeloma (MM) is the second most common hematological cancer in the United States. It is typically incurable, even with myeloablative chemotherapy and stem-cell transplantation. The epithelial mucin-1 (MUC1) glycoprotein is expressed by normal and malignant epithelial cells but has also been shown to be expressed by MM cells. MUC1 is a useful antigenic target in solid tumors for clinical diagnostic and therapeutic monoclonal antibody (mAb)-based approaches. The MA5 mAb, as well as other anti-MUC1 mAbs reactive with the MUC1 variable number tandem repeat domain, exhibited moderate to strong reactivity with both MM cell lines and clinical samples. To explore the biochemical nature and potential of MUC1 as an antigenic target in MM, studies were performed to: (a) compare the mRNA and the MUC1 glycoprotein species between epithelial cancer and MM cell lines; and (b) develop and use a human MM tumor xenograft model system to study the biodistribution of the MA5 mAb. MA5 mAb was strongly reactive with six of eight human MM cell lines by flow cytometry. In seven of eight MM patient samples (bone marrow and/or peripheral blood) reactivity was found in 10-90% of the cells, whereas normal control (n = 5) and leukemia and lymphoma (n = 5) cells showed only 0-6% reactivity. 125I-labeled MA5 whole-cell binding studies showed quantitatively similar amounts of binding between strongly positive MM lines and high-MUC1-expressing breast carcinoma lines. mRNA expression was assessed by Northern blotting and reverse transcription-PCR. MM cell lines were positive by both methods, with strong similarity in the sizes of the mRNAs and cDNAs that were obtained. Finally, biodistribution experiments were carried out with 131I-labeled MA5 versus a nonbinding control 125I-labeled mAb in a s.c. MM xenograft model. Selective MM tumor uptake of the MA5 mAb was demonstrated, with a potential for delivering a tumor radiation absorbed dose of 8540 cGy/mCi of injected dose compared with 3099 cGy/mCi of tumor-absorbed dose delivered by nonspecific antibody.

Animals↗

The major facilitator superfamily.

In 1998 we updated earlier descriptions of the largest family of secondary transport carriers found in living organisms, the major facilitator superfamily (MFS). Seventeen families of transport proteins were shown to comprise this superfamily. We here report expansion of the MFS to include 29 established families as well as five probable families. Structural, functional, and mechanistic features of the constituent permeases are described, and each newly identified family is shown to exhibit specificity for a single class of substrates. Phylogenetic analyses define the evolutionary relationships of the members of each family to each other, and multiple alignments allow definition of family-specific signature sequences as well as all well-conserved sequence motifs. The work described serves to update previous publications and allows extrapolation of structural, functional and mechanistic information obtained with any one member of the superfamily to other members with limitations determined by the degrees of sequence divergence.

Amino Acid Sequence↗

Rhesus thymic/liver xenografts in severe combined immunodeficient mice: immunologic reconstitution and intrathymic infection with simian immunodeficiency virus.

By serving as host recipients of xenografts from both humans and animals, severe combined immunodeficient (SCID) mice have become valuable to many laboratories interested in examining the pathophysiology of different diseases. To gain insight into the usefulness of the SCID mutation in retrovirus research, rhesus monkey fetal hematolymphoid tissues (liver and thymus) were used to construct a SCID-rhesus chimeric mouse (SCID-rh) and were engrafted in the renal capsule. The size and maturation of the thymic engrafts were monitored grossly, histologically, and immunologically. SCID mice were tolerant to rhesus tissues, and thymic engrafts contained thymocytes at different stages of maturation and differentiation that had morphologic features similar to age-matched rhesus thymus. Mature single positive CD2+, CD4+, and CD8+ T lymphocytes that were phenotypically similar to rhesus T lymphocytes were present at low levels (2% to 5%) in the peripheral blood and at moderately higher levels (7% to 15%) in the spleens of SCID-rh mice obtained between 12 and 15 weeks after thymus/liver engraftment. Within 3 weeks after engraftment, > 85% of the thymocytes in the thymic engrafts were immature double positive CD4+CD8+ T cells. The highest number of positive cells were seen in thymic engrafts obtained at 12 to 18 weeks. During these weeks, > 90% of the cells were double positive (CD2+CD4+, CD2+CD8+, and CD4+CD8+). After infection of the engrafted thymus tissue with simian immonodeficiency virus (SIVmac239), PCR analysis revealed successful viral infection of engrafts at 2 and 4 weeks after infection. No significant histopathologic and flow cytometric changes were observed in the thymic engrafts at 2 and 4 weeks after infection. An unrelated lesion of thymic lymphomas involving the SCID host thymus was seen in 12% of the mice. The data presented herein suggest that the SCID-rh is a valuable model for specific studies related to thymus-retrovirus interaction and that it could be used for further studies. The results are discussed in relation to current knowledge of thymus involvement during simian and human immunodeficiency virus infection.

Animals↗

Characterization of monoclonal antibody PAM4 reactive with a pancreatic cancer mucin.

A monoclonal antibody (MAb), PAM4, having reactivity with pancreatic carcinoma has been developed. PAM4 is an IgG1 immunoglobulin produced by immunization of mice with mucin purified from the xenografted RIP1 human pancreatic carcinoma. An immunohistochemical study of normal adult tissues showed the PAM4 reactive epitope to be restricted to the gastrointestinal tract and absent from normal pancreas. In neoplastic tissue, PAM4 was reactive with 85% of the pancreatic carcinomas, approximately half of the colon cancers and none of the breast, ovarian, prostate, renal and liver cancers. PAM4 was, in general, non-reactive with pancreatitis specimens whereas CA19.9 and DUPAN2 were strongly reactive with each one. Treatment of the mucin antigen by heating, reduction of disulfide bonds, or protease digestion abolished immunoreactivity with PAM4. Treatment of the mucin by neuraminidase or periodate oxidation reduced immunoreactivity but did not completely abolish it. Our data are consistent with the proposal that the PAM4 epitope is a conformationally dependent peptide epitope and that certain carbohydrate structures are necessary in order to maintain the correct peptide conformation. The high specificity and intense reactivity of PAM4 with pancreatic carcinoma tissue suggests that the antibody may prove useful for in vitro diagnostic assays as well as in vivo targeting of diagnostic and therapeutic agents.

Adult↗

Intrusion and apical resorption of mandibular incisors in Begg treatment: anchorage bend or curve?

A statistical evaluation of the apical root resorption in mandibular incisors following Begg treatment in one group with anchorage bends and another group with anchorage curves showed no statistical difference. Although the overbite reduction in both groups were similar, the anchorage curve group was statistically more efficient in incisor intrusion when compared to the anchorage bend group (p < 0.01).

Adolescent↗

Generation of a monoclonal antibody (G9) reactive with an organ-specific, tumor-associated epitope of human colon carcinoma.

A monoclonal antibody (G9), having an organ-specific and tumor-associated reactivity with colon carcinoma, has been generated. Monoclonal antibody G9 is an IgG1 immunoglobulin produced by immunization of mice with mucin which had been purified from a liver metastasis of a moderately differentiated human colon carcinoma. Examination of normal adult tissues, by enzyme immunoassay and immunohistochemical procedures, showed the G9-reactive epitope to be restricted to the gastrointestinal tract. Within the gastrointestinal tract the colon produced the highest amount of the epitope. A sharp, decreasing gradient of reactivity was observed, ending in the small intestine. Although the normal colonic epithelium did produce the G9-reactive determinant, there was a significant quantitative increase of the epitope in neoplastic colonic tissue; mucins derived from normal colon contained less than 10% of the specific epitope as compared with mucins derived from colon cancer tissues (P less than 0.01). In addition, a tumor xenograft contained 100 times the amount of epitope as did normal colonic tissue. By immunohistochemical procedures 70% of all colon carcinomas were positive. A relationship with differentiation was noted, with 80% of well differentiated and 83% of moderately differentiated tumors being positive, whereas only 1 of 6 poorly differentiated tumors were stained. The organ specificity was noted in neoplastic as well as normal tissues. Monoclonal antibody G9 was nonreactive with breast, lung, and ovarian tumors. The data suggest that at the level of sensitivity obtained by the immunoassays used, and within the range of tissues examined, monoclonal antibody G9 is organ specific and highly tumor associated in its reactivity.

Animals↗

Tooth extrusion effects on microvessel volumes, endothelial areas, and fenestrae in molar apical periodontal ligament.

Extrusive tooth loads, simulating short-term orthodontic movements, have not previously been used for transmission electron microscopic quantification of their effects on the periodontal ligament vessels. In this study, a continuous extrusive load of 1.0 N, applied to the rat maxillary first molar for 30 minutes, produced statistically significant changes in the microvascular bed of the tensioned apical periodontal ligament. The mean vascular volume, as a percentage of apical periodontal ligament volume, increased (p less than 0.01) in postcapillary-sized venules, venous capillaries, arterial capillaries, and terminal arterioles from 16.6% to 22.3%, 2.0% to 2.7%, 0.4% to 1.0%, and 1.0% to 2.5%, respectively. Mean endothelial surface area per cubic millimeter of apical periodontal ligament tissue increased (p less than 0.01) in postcapillary-sized venules from 16.8 to 25.7 x 10(6) microns 2/mm3, in venous capillaries from 3.0 to 4.8 x 10(6) microns 2/mm3, and in arterial capillaries from 0.7 to 1.5 x 10(6) microns 2/mm3. The number of fenestrae per square micron of endothelium in postcapillary-sized venules, venous capillaries, and arterial capillaries showed a mean increase from 0.02 to 0.07, 0.11 to 0.31, and 0.02 to 0.21 fenestrae/microns 2, respectively (p less than 0.01). Fenestrae per cubic millimeter of periodontal ligament tissue also demonstrated a statistically significant increase with extrusion (p less than 0.01) in postcapillary-sized venules from 0.37 to 1.55 x 10(6) fenestrae/mm3, in venous capillaries from 0.27 to 1.34 x 10(6) fenestrae/mm3, and in arterial capillaries from 0.02 to 0.22 x 10(6) fenestrae/mm3. Fenestrae in control vessels had a mean diameter of 54.2 +/- 0.56 nm (SE) compared with 61.1 +/- 0.7 nm in tensioned vessels (p less than 0.01). This investigation demonstrates multiple ultrastructural changes in the periodontal ligament microvascular bed after tooth extrusion.

Animals↗

Profile changes following orthodontic treatment of bimaxillary protrusion in adults with the Begg appliance.

Thirty-two adult oriental patients aged 18-26 years who sought treatment for their bimaxillary protrusion were treated with the Begg appliance following extraction of four first premolars. A cephalometric study was undertaken to determine the soft tissue changes in lip profile following treatment. Results show that the upper incisors were retracted by 5.6 mm +/- 0.8 mm and the lower incisors by 4.4 +/- 0.8 mm on the average. The nasolabial angle became more obtuse increasing from 80.7 degrees to 90.7 degrees. The upper lip and lower lip lengthened by 1.9 mm and 1.2 mm, respectively. The lower lip to 'E' line reduced from 7.5 mm to 3.7 mm. All the previous changes were statistically significant (p less than 0.01). The upper lip to upper incisor retraction was 1:2.2 while the lower lip to lower incisor retraction was 1:1.4. The correlation coefficients (r) were 0.72 (p less than 0.01) and 0.80 (p less than 0.01), respectively. The changes in the cants of mandibular and occlusal planes were statistically insignificant. This study shows that the Begg appliance has the ability to significantly reduce bimaxillary protrusions and thereby improve facial aesthetics.

Adolescent↗

Intralesional corticosteroid therapy for infantile hemangiomas.

Intralesional corticosteroid injections were performed in 31 hemangiomas in 30 infants aged 1 to 10 months at first injection. One to five injections were given, spaced 6 weeks apart. Lesions were located throughout the head and neck region, except one that was on the buttock. A mixture of betamethasone acetate and triamcinolone acetonide was used. Four lesions (13 percent) virtually disappeared, ten (32 percent) showed greater than 50 percent reduction in volume, ten (32 percent) showed definite but less than 50 percent reduction in volume, and seven (23 percent) showed little or no decrease in size. None showed further growth. All injections were performed without anesthesia, and there were not significant complications. We conclude that intralesional corticosteroid injections are safe and effective in properly selected infants with hemangiomas.

Betamethasone↗

Alignment of buccally displaced canines following premolar extractions: archwire or natural alignment?

The alignment times of buccally displaced maxillary canines following first premolar extractions were studied in 2 groups. The control group (n = 28) comprised of cases where no appliances were used while the experimental group (n = 28) had Begg brackets bonded on the upper teeth in conjunction with Sentalloy archwire. The imbrication indices (I.I.) of all canines were recorded for both groups prior to extraction and every 5 days after extractions until the canines aligned. The results indicated that there was no significant difference in the alignment rate at 30 days and 60 days between the 2 groups. However, the alignment rates at 90 and 120 days were both significantly faster in the experimental compared to the control group (p less than 0.01). While the alignment rates at 30, 60, 90 and 120 days in the experimental group followed a plateaued curve, the alignment rates in the control group followed a cusped curve. The results indicated that a 2 months self-alignment period following premolar extractions would be justified in most cases before banding.

Adolescent↗