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Biomedical subjects

M Lee

Publications and source records attributed to M Lee.

At least 613 records · Page 34Linked to original sources

Immunogold localization of high-affinity glucose transporter isoforms in normal rat kidney.

BACKGROUND: Facilitative glucose transporters (GLUT) have unique kinetic characteristics and distributions suited to the functions of the tissues in which they reside. However, little is known about their individual roles in renal glucose metabolism, and previous investigations of renal GLUT expression have been extensive only with respect to their mRNA levels. We provide here a complete analysis of three GLUT isoforms along the nephron using a sensitive immunodetection method. EXPERIMENTAL DESIGN: Normal rat kidneys were harvested, fixed in paraformaldehyde, and embedded in either paraffin or resin as required for immunogold labeling of individual GLUT Isoforms 1, 3, and 4. Samples were evaluated by light microscopy and selected regions analyzed by high resolution optical scanning with computer-assisted detection of immunogold-labeled GLUT at the subcellular level. We describe, compare, and related to the local patterns of glucose metabolism the cellular and subcellular expression patterns of these GLUT along the nephron. RESULTS: GLUT1 was most intensely labeled in the medullary thick ascending limbs of Henle, cortical collecting ducts, and inner medullary collecting ducts. In contrast, GLUT3 was most prominent in the inner medullary collecting ducts and GLUT4 in medullary thick ascending limbs of Henle. All three GLUT were detected in glomerular tufts, and GLUT1 was also detected in parietal epithelial cells. The predominant subcellular distributions in tubule cells were: basolateral and basolateral/cytoplasmic for GLUT1; basolateral and cytoplasmic for GLUT3; and perinuclear/cytoplasmic for GLUT4. GLUT 1 and 3 expressions were confirmed in specific regions by immunoblotting. CONCLUSIONS: 1) GLUT 1, 3, and 4 are expressed in both glomeruli and renal tubules. 2) The unique GLUT expression patterns along the renal tubules suggests unique functional roles for these isoforms. 3) The renal cortex demonstrates lesser labeling intensity for the high-affinity GLUT compared with the medulla, where higher rates of glucose oxidation and glycolytic metabolism are paralleled by higher GLUT labeling intensities.

Animals↗

Jejunal diverticulitis manifesting with abdominal wall abscess.

Jejunal diverticulosis is generally considered to be an innocuous condition, but serious complications can arise and lead to acute or chronic syndromes. In this report, we describe a case of jejunal diverticulitis presenting with an abdominal wall abscess. To our knowledge, this is the first documented case of jejunal diverticulitis complicated by fistula formation leading to the development of an abdominal wall abscess. Because jejunal diverticula generally localize at the mesenteric border and their perforation tends to result in intra-abdominal abscess formation, we speculate that the abdominal wall abscess described in our case here was due to adhesions of jejunal loops to the abdominal wall secondary to previous abdominal surgeries.

Abdominal Abscess↗

Genetic homogeneity in Sjögren-Larsson syndrome: linkage to chromosome 17p in families of different non-Swedish ethnic origins.

Sjögren-Larsson syndrome (SLS) is a rare, autosomal recessive disorder that is characterized by congenital ichthyosis, mental retardation, and spastic diplegia or tetraplegia. Three United States families, three Egyptian families, and one Israeli Arab family were investigated for linkage of the SLS gene to a region of chromosome 17. Pairwise and multipoint linkage analysis with nine markers mapped the SLS gene to the same region of the genome as that reported in Swedish SLS pedigrees. Examination of recombinants by haplotype analysis showed that the gene lies in the region containing the markers D17S953, D17S805, D17S689, and D17S842. D17S805 is pericentromeric on 17p. Patients in two consanguineous Egyptian families were homozygous at the nine marker loci tested, and another patient from a third family was homozygous for eight of the nine, suggesting that within each of these families the region of chromosome 17 carrying the SLS gene is identical by descent. Linkage of the SLS gene to chromosome 17p in families of Arabic, mixed European, Native American, and Swedish descent provides evidence for a single SLS locus and should prove useful for diagnosis and carrier detection in worldwide cases.

Alleles↗

[A HBV carrier with fulminant hepatitis complicated by ATL, multiple myeloma and thyroid cancer].

A 75-year-old female, born in Tochigi Prefecture, was admitted because of lumbago in August of 1991. The leukocyte count was 11,800/microliters with 22.5% atypical lymphocytes. We demonstrated a lymphocyte surface marker, ATL-associated antigen, and proviral DNA. We also identified 2.60 g/dl of serum monoclonal protein, found to be IgG, lambda type, and punched out lesions in the skull. We made a diagnosis of ATL. She was also a HBV carrier. The patient was treated with a modification of CHOP therapy, because of increasing atypical lymphocytes in the peripheral blood in November of 1992. She died of acute hepatitis, suddenly, in March of 1993. Autopsy revealed multiple myeloma, fulminant hepatitis and occult thyroid cancer in addition to ATL.

Acute Disease↗

Severe diarrhea due to Cokeromyces recurvatus in a bone marrow transplant recipient.

Cokeromyces recurvatus, a sporangiola-forming dimorphic fungus, is a rare cause of urogenital infection in humans. We report here a case of severe watery diarrhea due to C. recurvatus, which was treated successfully with high-dose oral nystatin therapy. We speculate that our patient was probably predisposed to infections due to opportunistic organisms, such as C. recurvatus, because of post-transplantation immunosuppression. To our knowledge, our patient represents the first documented case of diarrhea due to C. recurvatus in man, and this case highlights the potential pathogenic capability of this opportunistic organism in immunosuppressed patients.

Bone Marrow Transplantation↗

Colorectal cancer presenting with a cutaneous metastatic lesion on the scalp.

Cutaneous metastases occur rarely with colorectal adenocarcinoma, accounting for approximately 5 percent of all cutaneous metastases. Cutaneous metastases from colonic cancer are most often located on the abdominal skin. The case we describe here is unusual because colorectal adenocarcinoma rarely metastasizes to the scalp. A review of the English language literature revealed only six reported cases of cutaneous metastases from a colonic adenocarcinoma to the scalp.

Adenocarcinoma↗

Pilomatricoma of the testicle. An ossifying testicular tumor with hair matrix differentiation.

Teratomas of the testis account for 4% of all testicular tumors. Monodermal variants (eg, epidermal inclusion cysts) account for less than 1% of all these tumors. To our knowledge, we are reporting the first case of pilomatricoma of the testis, a monodermal teratomatous tumor of follicular differentiation, with secondary heterotopic ossification. The differential diagnosis of the characteristic "shadow" cells is discussed, and the significant literature on both benign and malignant ossifying lesions of the testis is reviewed.

Hair Diseases↗

Chart for preparation of dilutions of alpha-adrenergic agonists for intracavernous use in treatment of priapism.

Treatment of priapism with intracavernous alpha-adrenergic agonist vasoconstrictor agents is well accepted, particularly for patients with priapism secondary to intracavernous injections of papaverine, phentolamine and/or prostaglandin E1. Although many alpha-adrenergic agonists are commercially available, phenylephrine is preferred because it has potent and selective alpha 1-adrenergic stimulatory properties, which can decrease arteriolar flow to the cavernous sinusoids, and no beta 1-stimulatory effect, which could cause arrhythmias and angina in susceptible patients. Before intracavernous injection or irrigation an alpha-adrenergic agonist must be diluted. However, no readily available reference source lists this information. Therefore, we prepared a chart for extemporaneous preparation of dilutions of alpha-adrenergic agonists for intermittent injection or irrigation.

Adrenergic alpha-Agonists↗

Autoantibodies against 70-kDa heat shock proteins (HSP70) in allogeneic bone marrow transplant recipients.

We report that autoantibodies against the 70-kDa heat shock protein family (HSP70) were detected in allogeneic bone marrow transplant recipients. Antibodies to HSP70 family proteins were detected in three out of 14 recipients of an allogeneic marrow graft but in none of the seven patients receiving autologous peripheral blood stem cell transplant (PBSCT). Immunoblotting analysis combined with two-dimensional SDS-PAGE revealed that these patients had antibodies to a constitutive 73-kDa/pI 5.5 heat shock protein (HSP73) and to a stress-inducible 72-kDa/pI 5.6 protein (HSP72). This is the first report, to our knowledge, describing the presence of autoantibody against HSP73 in allogeneic marrow transplant recipients. Our results may provide additional insight into the etiology and the pathophysiology of allogeneic transplant-related disorders.

Adolescent↗

Cat 6 mo increases symptoms: online physician charting and more.

The physicians of the Children's Asthma Center and the computer scientists of Information Services at Texas Children's Hospital set out to design a system that is comfortable to use, structured enough to effectively measure outcomes, yet flexible enough to conserve the individuality of the patient. To achieve these goals, we examined how the differential diagnosis process is applied to clinical decision making and implemented it in a clinical workstation. Unique patterns representing the state of the patient's disease are formed by dynamically selecting pertinent sets of observations, assigning attributes to these observations, and describing relationships between observations and/or sets of observations.

Asthma↗

Adenocarcinoma of the colon presenting with a Sister Mary Joseph's nodule and Trousseau's syndrome.

We describe an unusual case of colon cancer presenting with two dermatologic manifestations of internal malignancies: Trousseau's syndrome and Sister Mary Joseph's nodule. Trousseau's syndrome is associated with 1 to 11 percent of internal malignancies, while 5 percent of colorectal carcinomas present with cutaneous metastases. Our case highlights the clinical significance of dermatologic signs of occult gastrointestinal malignancies.

Abdominal Neoplasms↗

Direction of manual force applied during assessment of stiffness in the lumbosacral spine.

OBJECTIVE: To measure the angle of applied manual force during assessment of posteroanterior stiffness in the lumbosacral spine. DESIGN: Ten physiotherapists with bachelor's degrees in physiotherapy and postgraduate qualifications in manipulative physiotherapy assessed stiffness at 6 lumbosacral vertebral levels in a controlled order. Two pain free subjects acted as patients. SETTING: A university biomechanics laboratory. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Applied force vector angles in the sagittal plane. RESULTS: The physiotherapists all varied the direction of the force they applied so that it was directed slightly toward the feet at the lower vertebral levels and more toward the head as they moved up the spine. There was a significant difference between the direction of the applied force vector angles at each vertebral level (p < .0001). The direction of force used was also significantly different for the two patients (p = .0067). The forces used by the physiotherapists were applied in directions more vertical than if forces had been applied in directions perpendicular to the surface curves of the two patients. CONCLUSION: The direction of the force applied by the physiotherapists in this study when assessing posteroanterior stiffness varied significantly between vertebral levels and seemed to take into account the individual shape of the lumbosacral curve of each patient.

Adult↗

Design, synthesis and biological evaluation of benzoic acid mustard derivatives of imidazole-containing and C-terminal carboxamide analogues of distamycin.

The synthesis, DNA binding and biological evaluation of two benzoic acid mustard derivatives of imidazole-containing analogues of distamycin in which the C-terminus is modified to contain a terminal carboxamide are described. The apparent DNA binding constants of compounds 5 and 6 were determined using an ethidium displacement assay, and the results showed that they do not have the AT sequence selectivity of distamycin and they show an acceptance for GC base pairs. Based on their pronounced binding to T4 DNA the data suggest that they bind to the minor groove of DNA. The cytotoxicities of compounds 5 and 6 in human chronic myeloid leukemia cells were determined using a MTT assay, and their IC50 values were 27 and 16 microM, respectively, and higher than the corresponding non-terminal carboxamide-containing analogues 3 and 4. Both compounds were however markedly more active than the non-targeted mustard BAM [N,N-bis (-2-chloroethyl)-4-aminobenzoic acid]. In the NCI panel of cell lines 5 gave a distinctly different pattern of tumor selectivity from 6. While these compounds were shown to alkylate DNA using a CD alkylation assay (35 +/- 10% for 5 and 85 +/- 10% for 6), they produced interstrand crosslinks poorly, even at 100 microM drug concentrations. Based on preliminary data from a polymerase stop assay compounds 3-6 gave different patterns of sequence selection monoalkylation which may contribute to their differing biological activities.

Antineoplastic Agents↗

Relationship between cytochrome P450 2E1 and acetone catabolism in rats as studied with diallyl sulfide as an inhibitor.

Previous studies have demonstrated that cytochrome P450 2E1 (P450 2E1) catalyzes the oxidation of acetone in vitro. The present study was designed to determine the importance of P450 2E1 in the catabolism of acetone in rats using diallyl sulfide (DAS) as an inhibitor of this enzyme. After a single intragastric dose of DAS, blood samples were collected from rats at different time points, and blood acetone concentrations were measured by gas chromatography. In a low DAS dose (50 mg/kg body weight) group, the maximum acetone level of 6-fold higher than the normal level was reached at 6 hr; the acetone level returned to normal at 48 hr. In a high dose (200 mg/kg) group, the maximum acetone level of 9-fold higher than the normal level was reached at 12 hr; the acetone level returned to normal at 60 hr. The turnover time and fractional turnover rate of elevated acetone were 15.8 +/- 0.5 hr and 0.054 +/- 0.001 hr-1, respectively, for the low dose, and 19.2 +/- 0.6 hr and 0.046 +/- 0.005 hr-1, respectively, for the high dose. In a chronic experiment, DAS (50 and 200 mg/kg, i.g.) was given to rats daily for 29 days, and elevated blood acetone levels were observed during the entire experimental period: 2.0 to 2.8 micrograms/mL for the low dose and 3.4 to 3.9 micrograms/mL for the high dose at 24 hr after the 1st, 7th, 14th and 28th doses versus 0.8 to 0.9 micrograms/mL for the control. The increase of blood acetone level was closely related to the decreases of N-nitrosodimethylamine (NDMA) demethylase activity and P450 2E1 content in liver microsomes. Consistent with the lack of cumulative effect from the multiple doses of DAS on acetone level, rather stable levels of the DAS metabolites, diallyl sulfoxide (45.0 micrograms/mL, range: 33.8 to 58.6 micrograms/mL) and diallyl sulfone (11.7 micrograms/mL, range: 6.9 to 15.6 micrograms/mL), were observed at 24 hr after the 1st, 7th, 21st and 28th doses with DAS (200 mg/kg) in the chronic experiment. It is likely that the inactivation and inhibition of P450 2E1 by DAS and its metabolites block the oxidation of acetone and cause its elevation in blood. The results strongly suggest an important role of P450 2E1 in acetone catabolism under physiological conditions.

Acetone↗

Cloning and characterisation of the human 5-HT5A serotonin receptor.

The human 5-HT5A serotonin receptor has been cloned. As with the mouse and rat 5-HT5A receptors, the gene consists of two coding exons separated by a large intron. The deduced amino acid sequence of the gene reveals a protein of 357 residues which shares 93% (nucleotide) and 84% (amino acid) identity to the cloned mouse 5-HT5A receptor. We have determined the tissue distribution of the receptor by reverse transcriptase-PCR and found expression in all regions of the brain examined with little or no expression in peripheral tissues. The receptor has been transiently expressed in Cos M6 cells and exhibits a pharmacological profile closely resembling the mouse and rat 5-HT5A receptors with high, specific binding for ergotamine and methiothepin.

Amino Acid Sequence↗

Suppression of the humoral immune response by cannabinoids is partially mediated through inhibition of adenylate cyclase by a pertussis toxin-sensitive G-protein coupled mechanism.

Cannabinoid compounds, including the major psychoactive component of marihuana, delta 9-tetrahydrocannabinol (delta 9-THC), have been widely established as being inhibitory on a broad array of humoral and cell-mediated immune responses. The presence of cannabinoid receptors has been identified recently on mouse spleen cells, which possess structural and functional characteristics similar to those of the G-protein coupled cannabinoid receptor originally identified in rat brain. These findings, together with those demonstrating that delta 9-THC inhibits adenylate cyclase in splenocytes, strongly suggest that certain aspects of immune inhibition by cannabinoids may be mediated through a cannabinoid receptor-associated mechanism. The objective of the present studies was to determine whether inhibition of adenylate cyclase is relevant to mouse spleen cell immune function and, if so, whether this inhibition is mediated through a Gi-protein coupled mechanism as previously described in neuronal tissue. Spleen cell activation by the phorbol ester phorbol-12-myristate-13-acetate (PMA), plus the calcium ionophore ionomycin, produced a rapid but transient increase in cytosolic cAMP, which was inhibited completely by immunosuppressive concentrations of delta 9-THC (22 microM) and the synthetic bicyclic cannabinoid CP-55940 (5.2 microM), which produced no effect on cell viability. Inhibition by cannabinoids of lymphocyte proliferative responses to PMA plus ionomycin and sheep erythrocyte (sRBC) IgM antibody-forming cell (AFC) response, was abrogated completely by low concentrations of dibutyryl-cAMP (10-100 microM). Inhibition of the sRBC AFC response by both delta 9-THC (22 microM) and CP-55940 (5.2 microM) was also abrogated by preincubation of splenocytes for 24 hr with pertussis toxin (0.1-100 ng/mL). Pertussis toxin pretreatment of spleen cells was also found to directly abrogate cannabinoid inhibition of adenylate cyclase, as measured by forskolin-stimulated accumulation of intracellular cAMP. These results indicate that inhibition of the sRBC AFC response by cannabinoids is mediated, at least in part, by inhibition of adenylate cyclase through a pertussis toxin-sensitive Gi-protein coupled cannabinoid receptor. Additionally, these studies further support the premise that cAMP is an important mediator of lymphocyte activation.

Adenylate Cyclase Toxin↗