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1.
Ren Fail ; 44(1): 217-223, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35166182

ABSTRACT

Background. Chronic peritoneal dialysis (PD) patients often develop hypokalemia but less commonly hyperkalemia.Methods. We explored incidence and mechanisms of hyperkalemia in 779 serum samples from 33 patients on PD for 1 - 59 months. Normal serum potassium concentration was defined as 3.5 - 5.1 meq/l.Results. Mean monthly serum potassium concentrations were normal (except for 1 month), but we observed hypokalemia (<3.5 meq/l) in 5% and hyperkalemia (>5.1 meq/l) in 14% of 779 serum samples. Incidence of hyperkalemia did not change over time on PD: Year 1 (15%), Year 2 (11%), Year 3 (19%), Years 4-5 (22%). Hyperkalemia was mostly modest but occasionally extreme [5.2-5.4 meq/l (55%), 5.5-5.7 meq/l (21%), 5.8-6.0 meq/l (10%), >6.0 meq/l (14%)]. Of 31 patients (2 excluded due to brief PD time), 39% displayed hyperkalemia only, 23% displayed hypokalemia only, and the remainder (38%) displayed both or neither. Comparing hypokalemia-only with hyperkalemia-only patients, we found no difference in potassium chloride therapy, medications interrupting the renin-angiotensin system, small-molecule transport status, and renal urea clearance. We compared biochemical parameters from the hypokalemic and hyperkalemic serum samples and observed lower bicarbonate concentrations, higher creatinine concentrations, and higher urea nitrogen concentrations in the hyperkalemic samples (p < 0.001 for each), without difference in glucose concentrations.Conclusion. We observed hyperkalemia 3 times as frequently as hypokalemia in our PD population. High-potassium diet, PD noncompliance, increased muscle mass, potassium shifts, and/or the daytime period without PD might contribute to hyperkalemia.


Subject(s)
Hyperkalemia/epidemiology , Hypokalemia/epidemiology , Peritoneal Dialysis/adverse effects , Adult , Aged , Female , Humans , Hyperkalemia/blood , Hyperkalemia/etiology , Hypokalemia/blood , Hypokalemia/etiology , Incidence , Male , Middle Aged , Potassium/blood , Retrospective Studies
2.
Mymensingh Med J ; 30(4): 1086-1092, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34605481

ABSTRACT

There are different types of gallbladder polyps having variable morphology and nature. Symptoms are vague and mostly diagnosed incidentally on abdominal ultrasound. Risk factors are many. Indications of surgery are not clearly understood due to lack of clinical evidence. This study was carried out to analyze the management of gallbladder polyp in our settings and review of available evidence. Patients who underwent clip less mini laparoscopic cholecystectomy for gallbladder polyp were included. Clinical data including short history, age, gender, parity, lab tests, ultrasound report and macroscopy were recorded during surgery. Histopathology reports collected later. Total of 112 patients with mean age 42.6 years (range 22-82), 74 of whom were female. Most of them (46.42%) were asymptomatic. Single polyp was in 69, multiple in 32 and polyp with stone in 8 patients. Sessile polyp was 74.10%. Average polyp size was 7.6mm. Cholesterol polyp was in 82 patients. Four out of 5 malignant polyps were single and sessile. Abdominal ultrasound is the mainstay of diagnosis of gallbladder polyp but size, location, morphology, number and presence of associated gallstone has to be mentioned. Symptomatic gallbladder polyp benefited from surgery. Polyps more than 6mm, single and sessile morphology above the age 50 should undergo cholecystectomy.


Subject(s)
Gallbladder Diseases , Gallbladder Neoplasms , Polyps , Adult , Aged , Aged, 80 and over , Female , Gallbladder/diagnostic imaging , Gallbladder/surgery , Gallbladder Diseases/diagnostic imaging , Gallbladder Diseases/epidemiology , Humans , Middle Aged , Polyps/diagnostic imaging , Polyps/surgery , Retrospective Studies , Ultrasonography , Young Adult
3.
Bone Joint J ; 98-B(9): 1283-8, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27587533

ABSTRACT

AIMS: This study analysed the clinical and radiological outcome of anatomical reduction of a moderate or severe stable slipped capital femoral epiphysis (SCFE) treated by subcapital osteotomy (a modified Dunn osteotomy) through the surgical approach described by Ganz. PATIENTS AND METHODS: We prospectively studied 31 patients (32 hips; 16 females and five males; mean age 14.3 years) with SCFE. On the Southwick classification, ten were of moderate severity (head-shaft angle > 30° to 60°) and 22 were severe (head-shaft angle > 60°). Each underwent open reduction and internal fixation using an intracapsular osteotomy through the physeal growth plate after safe surgical hip dislocation. Unlike the conventional procedure, 25 hips did not need an osteotomy of the apophysis of the great trochanter and were managed using an extended retinacular posterior flap. RESULTS: Clinical outcome was assessed using the range of movement and the Harris Hip (HHS), Western Ontario and McMaster Universities Osteoarthritis (WOMAC), and Merle d'Aubigné scores, while radiological measurements included slip and alpha angles. The mean duration of follow-up was 24.1 months (12 to 40). There was a significant improvement in all clinical and radiological measurements after treatment (p < 0.001). Post-operative major complications were one deep infection and one case of femoral head collapse. CONCLUSION: These findings suggest that a modified Dunn osteotomy carried out through Ganz approach is a safe and effective method of treating the stable SCFE with a high degree of slip. Cite this article: Bone Joint J 2016;98-B:1283-8.


Subject(s)
Hip Joint/surgery , Osteotomy/methods , Slipped Capital Femoral Epiphyses/surgery , Adolescent , Child , Child, Preschool , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Osteotomy/adverse effects , Postoperative Care/methods , Postoperative Complications/epidemiology , Postoperative Complications/physiopathology , Prospective Studies , Radiography/methods , Range of Motion, Articular/physiology , Recovery of Function , Risk Assessment , Severity of Illness Index , Slipped Capital Femoral Epiphyses/diagnosis , Time Factors , Treatment Outcome
4.
Mymensingh Med J ; 23(4): 676-85, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25481585

ABSTRACT

Febrile seizures are the most common type of seizure among children that can be prevented by using prophylactic drugs like Clobazam and Diazepam. The present prospective study was conducted in the Department of Pediatrics, Mymensingh Medical College Hospital and Community Based Medical College Hospital, Bangladesh over a period of 1 year from July 2012 to June 2013 to compare the effectiveness of intermittent Clobazam versus Diazepam therapy in preventing the recurrence of febrile seizures and assessed adverse effects of each drug. A total of 65 patients (32 children administered Clobazam and rest 33 children received Diazepam) of simple and complex febrile seizures aged 6 months to 5 years of both sexes were the study population. Data were collected by interview of the patients, clinical examination and laboratory investigations using the research instrument. Data were analyzed by using Chi-square (χ2) Test, Student's 't' Test and Fisher's Exact Test. For all analytical tests, the level of significance was set at 0.05 and p<0.05 was considered significant. The proportion of patients was higher between age 12-36 months and male was predominant in the both Clobazam and Diazepam groups. Over 31% of patients in Clobazam group who experienced episode of fever within 3 months, 40.6% within 6 months and 9.4% within 9 months compared to 36.4% in Diazepam group within 3 months, 45.5% within 6 months & 12.1% within 9 months after discharge from the hospital. Three (9.4%) patients in Clobazam group and 7(21.3%) in Diazepam group who experienced febrile convulsion during the follow up period. From the data adverse effects within 3 and 6 months experienced by the patient's drowsiness, sedation and ataxia were higher in Diazepam group than those in Clobazam group. However, within 9 months lethargy and irritability were somewhat higher in Clobazam group than those in Diazepam group. The mean duration of hospitalization was significantly higher in Diazepam group compared to Clobazam group (6.0±1.0 vs. 4.6±0.08 days, P<0.001). Seven (21.2%) out of 33 children with febrile seizures in Diazepam group had a history of recurrent seizures, whereas 3(9.4%) of 32 children in the Clobazam group. The risks of recurrent febrile seizure in the Diazepam group was 2.6 times greater compared to those in the Clobazam group (P=0.186). The result indicates that Clobazam is safe, efficacious, requires less frequent dosing and has less adverse effects such as drowsiness, sedation, ataxia and irritability as compared to Diazepam. So, Clobazam may be an alternative to Diazepam given intermittently for prevention of recurrent febrile seizures.


Subject(s)
Ataxia/chemically induced , Benzodiazepines , Diazepam , Lethargy/chemically induced , Seizures, Febrile , Age Factors , Anticonvulsants/administration & dosage , Anticonvulsants/adverse effects , Ataxia/prevention & control , Bangladesh/epidemiology , Benzodiazepines/administration & dosage , Benzodiazepines/adverse effects , Chi-Square Distribution , Child, Preschool , Clobazam , Diazepam/administration & dosage , Diazepam/adverse effects , Dose-Response Relationship, Drug , Drug Monitoring/methods , Female , Humans , Infant , Lethargy/prevention & control , Male , Prospective Studies , Recurrence , Risk Assessment , Seizures, Febrile/diagnosis , Seizures, Febrile/epidemiology , Seizures, Febrile/physiopathology , Seizures, Febrile/prevention & control , Sex Factors , Treatment Outcome
5.
Indian J Med Microbiol ; 32(1): 68-71, 2014.
Article in English | MEDLINE | ID: mdl-24399393

ABSTRACT

The aim of this study was to evaluate the rate of bacterial colonisation and catheter related blood stream infections (CRBSI) together with the antibiotic susceptibility patterns in a tertiary care hospital. CRBSI was detected with semi-quantitative and quantitative methods. The antimicrobial susceptible patterns of the isolated organisms were performed by Kirby Bauer disk diffusion method. The rate of catheter colonisation and CRBSI were 42.1% and 14% (16.1/1000 catheter days) respectively. The most common causative pathogens were Pseudomonas sp. (23.7%), Acinetobacter sp. (18.4%), Staphylococcus aureus (13.2%) and Enterobacteriaceae (10.5%). The rate of isolation of methicillin resistance S. aureus, imipenem resistant Pseudomonas sp. and extended spectrum ß lactamase producing Enterobacteriaceae were 60%, 44.0% and 100%. The result of this study would be useful for control and treatment of CRBSI.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteremia/epidemiology , Bacteria/drug effects , Bacteria/isolation & purification , Catheter-Related Infections/epidemiology , Bacteremia/microbiology , Bacteria/classification , Bangladesh/epidemiology , Catheter-Related Infections/microbiology , Catheters/microbiology , Humans , Microbial Sensitivity Tests , Prevalence , Tertiary Care Centers
6.
Mymensingh Med J ; 21(4): 696-701, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23134920

ABSTRACT

The use of oral mucous membrane graft onlay urethroplasty represents the most widespread method of bulbar urethral stricture repair. We investigated the short term result of oral mucous membrane graft placed on the ventral surface for management of bulbar urethral stricture. Patients with Bulbar urethral stricture of any length, infection free urinary tract and informed consent for oral mucosa harvesting and urethroplasty were selected for study. We enrolled 108 cases of bulbar urethral stricture patients from January 2004 to July 2009. The mean ± SD preoperative maximum flow rate of 5.2 ± 2.6 ml/sec and mean ± SD PVR 87 ± 58.3 ml were treated by substitution urethroplasty with oral mucous membrane by a single surgical team in a private hospital. Causes of stricture were trauma 26(24.1%), infection 58(53.7%), catheter induced 8(7.4%), post TURP 11(10.2%) and unknown 5(4.6%). Oral mucous membrane was harvested from the cheek or from the inner side of lower lip. Defect of the urethra displayed by longitudinal ventral urethrotomy and the graft was sutured over the edges of the incised urethral mucosa over a 14 Fr latex Foley's catheter. Spongiosum tissue was closed over the graft. Pericatheter urethrogram was performed in all cases to check for the anastomotic leakage and the Catheter was removed after 2 weeks of the procedure. After removal of catheter uroflowmetry & ultrasound scan of bladder were performed to estimate the maximum flow rate and post voidal residue. The patient was followed-up every 3 months with uroflowmetry & ultrasonography. The median (range) age of the patients was 32(21-72) years. Mean follow up period was 36 months (range 12-54). Mean ± SD stricture length was 3.7 ± 2.6 cm. The overall success rate was 91.7%. Mean ± SD flow rate was 23 ± 4.2 ml/sec, mean ± SD post void residue was 25 ± 15.5 ml and patient quality of life (QOL) was excellent in almost all patients. Overall complications were seen in 9(8.3%) cases. Of which, restricture occurred in 6 patients; periurethral fistulae seen in 2 cases and per urethral bleeding in 1 patient. No significant complications were observed at the donor site. Oral numbness and mild discomfort complained by 67.6% patients which were managed by reassurance only. In our experience ventral placement of oral mucous membrane graft along with spongioplasty is a very easy procedure with very encouraging short term result.


Subject(s)
Free Tissue Flaps , Mouth Mucosa/transplantation , Urethral Stricture/surgery , Adult , Aged , Humans , Male , Middle Aged , Postoperative Complications , Young Adult
7.
Gut ; 52(10): 1419-23, 2003 Oct.
Article in English | MEDLINE | ID: mdl-12970133

ABSTRACT

BACKGROUND: The enkephalins, endogenous opiate substances, act as neurotransmitters along the entire digestive tract where they elicit intestinal antisecretory activity without affecting intestinal transit time or motility. Racecadotril, through inhibition of enkephalinase, reinforces the physiological activity of endogenous enkephalins and, therefore, shows intestinal antisecretory activity. AIM: We conducted the study to determine the role of racecadotril as an adjunct to the standard treatment of cholera in adults. METHODS: The study was a double blind, randomised, placebo controlled clinical trial involving 110 adult male cholera patients who received either racecadotril or placebo in addition to standard cholera treatment. The major outcome measures (stool output, oral rehydration solution (ORS) intake, requirements for unscheduled intravenous fluid infusion, and duration of diarrhoea) were compared between the groups. RESULTS: Of 110 patients enrolled, 54 received racecadotril and 56 received placebo. Admission clinical characteristics were comparable between the groups. There was no significant difference in (mean (SD)) total stool output (racecadotril v placebo 315 (228) v 280 (156) g/kg), total ORS intake (390 (264) v 369 (240) ml/kg), or duration of diarrhoea (35 (15) v 32 (13) hours) between the groups. Clinical success, defined as resolution of diarrhoea within 72 hours of initiation of study intervention, was similar in both groups (racecadotril v placebo 96% v 89%). The number of patients receiving unscheduled intravenous infusions was not significantly different between the groups (racecadotril v placebo 22% v 14%). No drug related adverse effect was noted. CONCLUSION: The study demonstrated that racecadotril therapy, although found to be safe, does not provide additional benefit in the treatment of severe cholera in adults.


Subject(s)
Antidiarrheals/therapeutic use , Cholera/drug therapy , Thiorphan/analogs & derivatives , Thiorphan/therapeutic use , Vibrio cholerae , Acute Disease , Adolescent , Adult , Chemotherapy, Adjuvant , Chi-Square Distribution , Double-Blind Method , Humans , Male , Middle Aged , Statistics, Nonparametric
8.
Folia Microbiol (Praha) ; 47(5): 545-50, 2002.
Article in English | MEDLINE | ID: mdl-12503402

ABSTRACT

Four Frankia-Casuarina endosymbiont strains were tested for their infectivity and effectiveness on C. equisetifolia plants after 1 d, 3 and 6 months of Frankia storage at 7, 28 and 40 degrees C as liquid-cultures and polyacrylamide gel (PAG)-immobilized inocula. At lower temperature the number of nodules was the same or higher than control for liquid inocula except after 6 months of storage. For the PAG-entrapped Frankia lower numbers of nodules were recorded due to the use of high Frankia titers. In general, the results showed comparable plant dry mass, total nitrogen, root to shoot and nodules to plant ratios at lower temperature treatments. Increasing time and temperature was accompanied with reduced infectivity and effectiveness on inoculated plants. No nodulation was scored on plants inoculated with liquid and PAG-entrapped inocula stored at 40 degrees C for 6 months; subsequently, plant growth was inhibited. The variations in results obtained for different strains and treatments lead to variations in plant nitrogen-fixing ability. The use of PAG as a carrier for different Frankia strains is suggested; the recommended storage temperature for PAG-immobilized Frankia in 7-28 degrees C for up to 3 months.


Subject(s)
Acrylic Resins , Frankia/pathogenicity , Plants/microbiology , Symbiosis , Temperature , Culture Media , Frankia/growth & development , Microbiological Techniques , Plant Roots/microbiology
9.
J Biol Chem ; 276(23): 20750-7, 2001 Jun 08.
Article in English | MEDLINE | ID: mdl-11278829

ABSTRACT

Translation initiation is a key point of regulation in eukaryotic gene expression. 4E-binding proteins (4E-BPs) inhibit initiation by blocking the association of eIF4E with eIF4G, two integral components of the mRNA cap-binding complex. Phosphorylation of 4E-BP1 reduces its ability to bind to eIF4E and thereby to compete with eIF4G. A novel combination of biophysical and biochemical tools was used to measure the impact of phosphorylation and acidic side chain substitution at each potentially modulatory site in 4E-BP1. For each individual site, we have analyzed the effects of modification on eIF4E binding using affinity chromatography and surface plasmon resonance analysis, and on the regulatory function of the 4E-BP1 protein using a yeast in vivo model system and a mammalian in vitro translation assay. We find that modifications at the two sites immediately flanking the eIF4E-binding domain, Thr(46) and Ser(65), consistently have the most significant effects, and that phosphorylation of Ser(65) causes the greatest reduction in binding affinity. These results establish a quantitative framework that should contribute to understanding of the molecular interactions underlying 4E-BP1-mediated translational regulation.


Subject(s)
Carrier Proteins , Models, Molecular , Phosphoproteins/physiology , Protein Biosynthesis/physiology , Adaptor Proteins, Signal Transducing , Amino Acid Sequence , Amino Acid Substitution , Animals , Aspartic Acid/chemistry , Aspartic Acid/metabolism , Cell Cycle Proteins , Chromatography, Affinity , Glutamic Acid/chemistry , Glutamic Acid/metabolism , Mammals , Molecular Sequence Data , Phosphoproteins/chemistry , Phosphoproteins/metabolism , Phosphorylation , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Surface Plasmon Resonance
10.
Am J Ophthalmol ; 129(3): 398-401, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10704568

ABSTRACT

PURPOSE: Cox-2, a prostaglandin synthase, is overexpressed in colorectal cancers and is involved in angiogenesis as well as in tumorigenesis. In this study, we investigate the expression of Cox-2 in retinoblastoma. METHODS: Twenty-nine formalin-fixed retinoblastoma specimens were examined by the labeled-streptavidin-biotin method using anti-Cox-2 antibody. RESULTS: Cox-2 positive immunoreactions were observed in 28 (96%) of 29 retinoblastomas specimens. CONCLUSION: This preliminary study suggests the overexpression of Cox-2 in both differentiated and undifferentiated retinoblastoma and its possible role in tumorigenesis.


Subject(s)
Isoenzymes/biosynthesis , Peroxidases/biosynthesis , Prostaglandin-Endoperoxide Synthases/biosynthesis , Retinal Neoplasms/enzymology , Retinoblastoma/enzymology , Child, Preschool , Cyclooxygenase 2 , Female , Humans , Immunoenzyme Techniques , Infant , Male , Membrane Proteins , Retinal Neoplasms/pathology , Retinoblastoma/pathology
11.
Jpn J Ophthalmol ; 44(2): 179-82, 2000.
Article in English | MEDLINE | ID: mdl-10715389

ABSTRACT

PURPOSE: Orbital cholesterol granuloma in a 51-year-old man is described. METHODS: Computed tomography (CT) and magnetic resonance imaging (MRI) were done. RESULTS: Both studies showed a mass in the left orbit, with evidence of orbital roof destruction in the CT scan. On the basis of clinical and imaging findings, a diagnosis was made of malignant orbital tumor with destruction of the lateral orbital roof. Surgical exploration revealed a thickly encapsulated mass densely adherent to the left superior orbital bone and periosteum. Although the dura mater was intact, bone destruction in the lateral orbital roof was seen. The entire mass was successfully excised and histopathological evaluation was performed. Histopathology showed numerous inflammatory cells, blood degradation products, and cholesterol clefts. The absence of epithelial elements led to the diagnosis of cholesterol granuloma. CONCLUSIONS: Care must be taken to differentiate cholesterol granuloma from malignant orbital tumor. CT scan and MRI imaging seem well-suited to detecting the characteristic findings of cholesterol granuloma.


Subject(s)
Cholesterol/metabolism , Granuloma/diagnostic imaging , Granuloma/metabolism , Orbit/diagnostic imaging , Orbital Diseases/diagnostic imaging , Orbital Diseases/metabolism , Granuloma/pathology , Humans , Male , Middle Aged , Orbit/pathology , Orbital Diseases/pathology , Tomography, X-Ray Computed
12.
Folia Microbiol (Praha) ; 45(2): 153-6, 2000.
Article in English | MEDLINE | ID: mdl-11271824

ABSTRACT

Growth of three Frankia strains associated with roots of Casuarina tree, treated with different concentrations of metal ions, was measured as total protein content. One strain was highly resistant to different aluminum ion concentrations up to 10 mmol/L. The other two strains were more sensitive to the higher aluminum concentrations (1.25-10 mmol/L). Growth inhibition by cobalt and lead concentrations varied, depending on the tested strain. Stimulation occurred only at cobalt concentrations of 0.33 and 0.65 mmol/L for one strain.


Subject(s)
Aluminum/pharmacology , Bacteria/drug effects , Cobalt/pharmacology , Lead/pharmacology , Ions/pharmacology , Plant Roots/microbiology , Soil Microbiology , Trees/microbiology
13.
Clin Diagn Lab Immunol ; 6(6): 812-8, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10548569

ABSTRACT

The immunoglobulin subclass responses to homologous lipopolysaccharide (LPS) and to cholera toxin (CT) in adult patients infected with Vibrio cholerae O1 and V. cholerae O139 were studied. LPS-specific antibody-secreting cells (ASC) of both the immunoglobulin A1 (IgA1) and IgA2 subclasses were seen, with the IgA1 ASC response predominating in both V. cholerae O1- and O139-infected patients. For antibodies in plasma, by day 11 after onset of disease, all V. cholerae O1- infected patients responded to homologous LPS with the IgA1 subclass (P = 0.001), whereas fewer (68%) responded with the IgA2 subclass (P = 0.007). About 89% of V. cholerae O139-infected patients responded with the IgA1 subclass (P = 0.003), and only 21% responded with the IgA2 subclass (not significant [NS]). Both groups of cholera patients showed significant increases in LPS-specific IgG1, IgG2, and IgG3 antibodies in plasma. In feces, the response to homologous LPS occurred in both groups of patients with the IgA1 and IgA2 subclasses, with 55 to 67% of patients showing a positive response. V. cholerae O1- and O139-infected patients showed CT-specific ASC responses of the different IgG and IgA subclasses in the circulation, and the pattern followed the order IgG1 > IgA1 > IgG2 > IgA2, with low levels of IgG3 and IgG4 ASC. Plasma anti-CT antibody responses in all subclasses were seen by day 11 after onset of disease. Although there were no increases in CT-specific ASC of the IgG3 (NS) and IgG4 (NS) subtypes, there were significant increases of these two subclasses in plasma (P

Subject(s)
B-Lymphocytes/immunology , Cholera Toxin/immunology , Cholera/immunology , Lipopolysaccharides/immunology , Vibrio cholerae/immunology , Adolescent , Adult , Antibodies, Bacterial/analysis , Antibodies, Bacterial/blood , Antigens, Bacterial/immunology , Feces/microbiology , Humans , Immunoglobulin A/analysis , Immunoglobulin A/blood , Immunoglobulin G/analysis , Immunoglobulin G/blood , Male , Middle Aged
14.
EMBO J ; 18(14): 4068-75, 1999 Jul 15.
Article in English | MEDLINE | ID: mdl-10406811

ABSTRACT

Eukaryotic translation initiation involves recognition of the 5' end of cellular mRNA by the cap-binding complex known as eukaryotic initiation factor 4F (eIF4F). Initiation is a key point of regulation in gene expression in response to mechanisms mediated by signal transduction pathways. We have investigated the molecular interactions underlying inhibition of human eIF4E function by regulatable repressors called 4E-binding proteins (4E-BPs). Two essential components of eIF4F are the cap-binding protein eIF4E, and eIF4G, a multi-functional protein that binds both eIF4E and other essential eIFs. We show that the 4E-BPs 1 and 2 block the interaction between eIF4G and eIF4E by competing for binding to a dorsal site on eIF4E. Remarkably, binding of the 4E-BPs at this dorsal site enhances cap-binding via the ventral cap-binding slot, thus trapping eIF4E in inactive complexes with high affinity for capped mRNA. The binding contacts and affinities for the interactions between 4E-BP1/2 and eIF4E are distinct (estimated K(d) values of 10(-8) and 3x10(-9) for 4E-BP1 and 2, respectively), and the differences in these properties are determined by three amino acids within an otherwise conserved motif. These data provide a quantitative framework for a new molecular model of translational regulation.


Subject(s)
Carrier Proteins/metabolism , Eukaryotic Initiation Factors , Peptide Initiation Factors/antagonists & inhibitors , Phosphoproteins/metabolism , RNA Caps/metabolism , RNA-Binding Proteins/metabolism , Response Elements/genetics , Adaptor Proteins, Signal Transducing , Allosteric Regulation , Amino Acid Sequence , Binding Sites , Carrier Proteins/chemistry , Carrier Proteins/genetics , Cell Cycle Proteins , Eukaryotic Initiation Factor-4E , Eukaryotic Initiation Factor-4F , Eukaryotic Initiation Factor-4G , Humans , Kinetics , Models, Molecular , Molecular Sequence Data , Mutation , Peptide Initiation Factors/chemistry , Peptide Initiation Factors/genetics , Peptide Initiation Factors/metabolism , Phosphoproteins/chemistry , Phosphoproteins/genetics , Protein Binding , RNA/genetics , RNA/metabolism , RNA Caps/genetics , RNA-Binding Proteins/chemistry , RNA-Binding Proteins/genetics , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/metabolism , Repressor Proteins/chemistry , Repressor Proteins/genetics , Repressor Proteins/metabolism , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/growth & development
15.
J Biol Chem ; 274(6): 3261-4, 1999 Feb 05.
Article in English | MEDLINE | ID: mdl-9920863

ABSTRACT

4E-binding proteins (4E-BPs) are believed to have important regulatory functions in controlling the rate of translation initiation in mammalian cells. They do so by binding to the mRNA cap-binding protein, eIF4E, thereby inhibiting formation of the cap-binding complex, a process essential for cap-dependent translation initiation. We have reproduced the translation-repressive function of human 4E-BP1 in yeast and find its activity to be dependent on substitution of human eIF4E for its yeast counterpart. Translation initiation and growth are inhibited when human 4E-BP1 is expressed in a strain with the human eIF4E substitution, but not in an unmodified strain. We have compared the relative affinities of human 4E-BP1 for human and yeast eIF4E, both in vitro using an m7GTP cap-binding assay and in vivo using a yeast two-hybrid assay, and find that the affinity of human 4E-BP1 for human eIF4E is markedly greater than for yeast eIF4E. Thus yeast eIF4E lacks structural features required for binding to human 4E-BP1. These results therefore demonstrate that the features of eIF4E required for binding to 4E-BP1 are distinct from those required for cap-complex assembly.


Subject(s)
Carrier Proteins , Phosphoproteins/metabolism , Protein Biosynthesis , Repressor Proteins/metabolism , Adaptor Proteins, Signal Transducing , Amino Acid Sequence , Binding Sites , Cell Cycle Proteins , Eukaryotic Initiation Factor-4E , Humans , Peptide Initiation Factors/metabolism , Phosphoproteins/genetics , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Repressor Proteins/genetics , Saccharomyces cerevisiae/genetics
16.
Ophthalmologica ; 211(1): 44-8, 1997.
Article in English | MEDLINE | ID: mdl-8958531

ABSTRACT

Eccrine adenocarcinoma of the lacrimal sac region is described in a 48-year-old man. The case was first diagnosed as an adenocarcinoma and removed by dacryocystectomy, but unfortunately the neoplasm recurred after a period of 1 year. Examinations with periodic acid-Schiff (PAS) and several antibodies indicate that this is a hitherto undescribed eccrine adenocarcinoma, and finally the case was managed by orbital exenteration. This is the first case of eccrine adenocarcinoma of the lacrimal sac region to be documented in the world literature.


Subject(s)
Adenocarcinoma/diagnosis , Eccrine Glands/pathology , Lacrimal Apparatus Diseases/diagnosis , Sweat Gland Neoplasms/diagnosis , Adenocarcinoma/surgery , Biopsy , Eccrine Glands/surgery , Follow-Up Studies , Humans , Lacrimal Apparatus Diseases/surgery , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/surgery , Reoperation , Sweat Gland Neoplasms/surgery
17.
Ophthalmologica ; 211(6): 351-3, 1997.
Article in English | MEDLINE | ID: mdl-9380352

ABSTRACT

Specimens of 24 enucleated eyes from patients with retinoblastomas in situ were examined by labelled streptavidin biotin (LSAB) method to ascertain the distribution of S-100 protein and compared with 28 normal developing eyes. Polyclonal anti-S-100 antiserum and monoclonal alpha and beta chain anti-S-100 antibodies were used in this study. In the normal retina a weak reaction was observed in astrocytes and ganglion cells at 24 gestational weeks (GW) and there was an increase in the intensity of staining with increasing age. In the morphologically normal retina with retinoblastoma, astrocytes, ganglion cells and Müller cells showed positive reactions for S-100 protein. Examined tumors showed S-100 protein-positive glial cells that were interpreted as reactive astrocytes. No reaction product was detected in the tumor cells. These findings support the concept that in the retinoblastoma, only glial cells are positive for S-100 protein.


Subject(s)
Retina/chemistry , Retinal Neoplasms/chemistry , Retinoblastoma/chemistry , S100 Proteins/analysis , Antibodies, Monoclonal , Biomarkers, Tumor/analysis , Humans , Immunohistochemistry , Neuroglia/chemistry , Neuroglia/cytology , Retina/cytology , Retinal Neoplasms/pathology , Retinoblastoma/pathology , S100 Proteins/immunology
18.
Kobe J Med Sci ; 42(3): 151-61, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8973084

ABSTRACT

The clinical features of three cases of retinoblastoma and the histopathological and immunocytochemical findings of the retinoblastoma specimens of these patients are described. The other eye of each patient was normal. There was no family history of retinoblastoma. Fundal examination disclosed white masses in the posterior segments of the eyes. B-scan ultrasonography showed echo dense areas in the masses. Orbital tomograms showed no evidence of tissue densities. There was neither extraocular extension nor optic nerve involvement. Immunocytochemistry of paraffin-embedded tissues of the neoplasms revealed immunoreactivity with antibodies against S-100 protein, glial fibrillary acidic protein(GFAP), vimentin, neuron-specific enolase(NSE) and bcl-2. S-100, GFAP and vimentin were positive only for glial elements(reactive astrocytes) and, NSE and bcl-2 for almost all tumor cells. These findings support the previous reports that the majority of retinoblastomas are sporadic. The results of this study also support the views that retinoblastomas are composed of neuron-committed cells.


Subject(s)
Eye Neoplasms/diagnosis , Retinoblastoma/diagnosis , Child, Preschool , Eye Neoplasms/pathology , Eye Neoplasms/surgery , Female , Glial Fibrillary Acidic Protein/analysis , Humans , Immunohistochemistry , Infant , Male , Retinoblastoma/pathology , Retinoblastoma/surgery , S100 Proteins/analysis , Vimentin/analysis , Visual Acuity
19.
Kobe J Med Sci ; 42(3): 163-72, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8973085

ABSTRACT

A male child of 1-year, 6-month-old had a history of leukocoria of the left eye for approximately three months prior to admission into our facility. No abnormality was found in the right eye. There was negative family history of retinoblastoma. Ophthalmoscopy revealed a white mass extending from the supero-posterior part of the left globe to the posterior surface of the lens. Orbital tomograms showed no intraocular tissue densities in the mass but a B-scan ultrasound showed an echo dense area of the mass. Histopathologically areas of photoreceptor differentiation and Flexner-Wintersteiner rosettes were observed in the tumor mass by light microscope. Transmission electron microscopy disclosed the presence of prominent mitochondria on the luminal side of the cells forming rosettes and these were believed to be the component parts of the inner-segments of the photoreceptor cells. The results of this study indicate a predominant neuronal nature of the neoplastic cells with photoreceptor-like differentiation.


Subject(s)
Eye Neoplasms/diagnosis , Eye Neoplasms/ultrastructure , Retinoblastoma/diagnosis , Retinoblastoma/ultrastructure , Cell Differentiation , Cytoplasm/ultrastructure , Eye Neoplasms/surgery , Humans , Infant , Male , Microscopy, Electron , Mitochondria/ultrastructure , Neurons/ultrastructure , Photoreceptor Cells/ultrastructure , Retinoblastoma/surgery
20.
Kobe J Med Sci ; 42(2): 111-7, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8699782

ABSTRACT

We have studied the expression of glial fibrillary acidic protein(GFAP), an astrocyte specific protein in the normal developing human retina using anti-GFAP antibody. GFAP positive cells were first detected at 24 gestational weeks(GW) in the nerve fiber and ganglion cell layers in the vicinity of the optic disc. Over subsequent weeks, GFAP positive cells covered larger regions of the retina. Some of the processes of these cells terminated in sucker like end-feet upon blood vessels of the nerve fiber layer. A second population of GFAP positive cells existed as perivascular glia in the nerve fiber layer in the early stage of fetal development. In the adult retina perivascular glia were found on vessels throughout the nerve fiber and in the inner portion of the inner plexiform layers. Staining of Müller cells end-feet was obtained only in the adult retina. These results support the views that in the human retina, GFAP positive cells first appear at 24 GW in the region near the optic disc, covering the whole retina at subsequent ages.


Subject(s)
Aging/physiology , Glial Fibrillary Acidic Protein/metabolism , Retina/metabolism , Adolescent , Adult , Child , Child, Preschool , Gestational Age , Humans , Immunochemistry , Infant , Infant, Newborn
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