Adult ; Diagnostic Errors ; Fatal Outcome ; Humans ; Male ; Pulmonary Alveolar Proteinosis ; complications ; Silicosis ; complications

Humans ; Infant ; Lead Poisoning, Nervous System, Childhood ; diagnosis ; therapy ; Male

OBJECTIVETo report the results of clinical characteristics, enzyme activity determination and mutation analysis of GLB1 gene in a Chinese patient with mucopolysaccharidosis (MPS) type IVB (Morquio B disease).

METHODA 14-year-old Chinese boy with MPS type IVB was firstly diagnosed by blood leucocytes galactosamine-6-sulfate sulfatase (GALNS) and β-galactosidase (GLB1) determination, who was characterized by short stature, multiplex skeletal abnormalities, difficulty in walking. PCR-sequencing analysis was applied to detect the mutations in GLB1 of the patient.

RESULTThe patient was characterized by dwarfism, pectus carinatum, kyphosis, normal intelligence, and no neurologic damage of spasms, linguistic capacity and so on. The patient had normal GALNS enzyme activity and very low GLB1 enzyme activity [5.03 nmol/(h·mg) vs. normal value 118 - 413 nmol/(h·mg) ] in leukocytes. A compound heterozygous missense mutations c.442C > T(p.R148C)/c.1454A > G(p.Y485C) in GLB1 gene were detected in this patient. The mutation p.Y485C is a novel variant. With the method of gene analysis of new variant, the mutation p.Y485C was considered to be a pathogenic mutation.

CONCLUSIONThe MPS IVB patient showed severe multiple skeletal deformities, normal intelligence, no neurologic damage and very low GLB1 enzyme activity, who carries compound heterozygous mutations p.R148C/p.Y485C. The mutation p.Y485C in GLB1 gene may be a novel pathologic mutation of MPS type IVB.

Adolescent ; Amino Acid Sequence ; Asian Continental Ancestry Group ; genetics ; Chondroitinsulfatases ; genetics ; metabolism ; DNA Mutational Analysis ; Humans ; Joints ; pathology ; Male ; Molecular Sequence Data ; Mucopolysaccharidosis IV ; enzymology ; genetics ; pathology ; Mutation, Missense ; Pedigree ; Polymerase Chain Reaction ; Radiography ; Spine ; diagnostic imaging ; pathology ; beta-Galactosidase ; genetics ; metabolism

To find the relationship between myelodysplastic syndrome (MDS) and refractory monolineage cytopenia, thirteen cases of MDS with early presentation of monolineage refractory cytopenia were analyzed retrospectively. The results were as follows: (1) The percentage of 13 cases with refractory monolineage cytopenia were 5.9% of the total 219 MDS patients in the past 10 years. (2) The median time of patients with monlineage cytopenia to M DS diagnosed was 48.5 +/- 55.3 months. The median times from monolineage cytopenia to MDS diagnosed for patients with neutropenia, erythrocytopenia and thrombocytopenia were 12.5 +/- 9.5 months, 53.8 +/- 54.6 months and 59.2 +/- 65.5 months, respectively. (3) The common characteristics of 13 cases were as follows: (a) the macrocytic erythrocytes in peripheral blood and the percentage of intermediate and late erythroblast in bone marrow were increased; (b) occasionally few cells with dysplasia could be found; (c) all patients with erythrocytopenia and thrombocytopenia transformed to RA and RAS while the most of patients with neutropenia transformed to RAEB subtype; (d) autoantibody could be found in part of the patients. It is concluded that some of refractory monolineage cytopenias in essence are the early states of MDS.
Adolescent ; Adult ; Aged ; Anemia, Hemolytic ; diagnosis ; Child ; Diagnosis, Differential ; Female ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; diagnosis ; Neutropenia ; diagnosis ; Purpura, Thrombocytopenic, Idiopathic ; diagnosis ; Retrospective Studies

OBJECTIVETo evaluate the diagnostic value of serum galactomannan antigen (GM) and (1→3)-β-D-glucan antigen (BG) assay in invasive fungal infections (IFI) in the patients with hematologic malignancies and the role in monitoring therapeutic response.

METHODSFifty one patients with hematological malignancies met the criteria for inclusion: (1) body temperature above 38°C for 48 hours, (2) failure to respond to broad-spectrum antibiotic treatment, or (3) temperature rose again after the responded drop. Blood samples were collected twice at the first week, then once a week in at least four weeks. The double antibody sandwich enzyme-linked immunosorbent assay (ELISA) and colorimetric assay were used for detecting GM and BG. The positive GM test is defined as two consecutive tests at different time GM value > 0.5 or > 0.8 and the positive G test is defined as BG value > 80 pg/ml. The patients were assigned into four groups as proven, probable, possible, and non-fungal infection respectively, and 21 normal volunteers were as controls.

RESULTSTwo hundred and forty serum samples were collected from 51 patients including 2 of proven IFI, 26 probable IFI, 17 possible IFI and 6 non-fungal infection. The true-positive group including the proven and probable groups, and true negative group was the non-fungal infection group. GM tests were positive in 21 of 28 cases in true positive group, and only one of 6 cases in non-fungal infection. The sensitivity, specificity, positive predictive value and negative predictive value were 75%, 83.3%, 95.5% and 41.7%, respectively. G tests were positive in all 28 cases of the true positive group, and 4 in 6 non-fungal infection cases. The sensitivity, specificity, positive predictive value and negative predictive value were 100%, 33.3%, 87.5% and 100%, respectively. G test is more sensitive than GM test (P = 0.015), but there was no significant difference in specificity of the two tests (P = 0.242). In 19 of 21 patients with GM test positive, anti-fungal treatment was effective, and GM value gradually decreased to negative, two invalid patients were persistent with GM test positive. After two weeks treatment, the average GM value was significantly lower in the effective group than in the ineffective group (P < 0.05). BG values in the responded patients showed a gradual decline similar to that of GM values, but not to negative. The changes of BG value in ineffective group varied with a trend upward. The changes in BG value had no relation with treatment effectiveness.

CONCLUSIONSSerum GM and BG antigens detection provides strong evidence for early diagnosis of IFI. Combination of GM and G tests can improve the diagnostic specificity and reduce the false positive GM test seems superior to G test for monitoring GM and BG values during treatment.

Adult ; Aged ; Aged, 80 and over ; Antigens, Fungal ; blood ; immunology ; Female ; Hematologic Neoplasms ; immunology ; microbiology ; Humans ; Male ; Mannans ; immunology ; Middle Aged ; Mycoses ; blood ; immunology ; Young Adult ; beta-Glucans ; immunology

OBJECTIVETo investigate the accumulation of advanced glycation end products (AGE) and the inflammatory response of skin and wound in diabetic patients, and to analyze their relationship in vitro.

METHODSHistological staining and immunohistochemical staining was respectively performed on skin and wound tissue specimens collected from 10 patients with Type II diabetes mellitus (diabetes group) and 12 non-diabetic patients with skin injury (control group) to observe the arrangement of collagen and the distribution of inflammatory cells, and to determine the expression levels of AGE and its receptor (RAGE). Malondialdehyde (MDA) levels in skin and wound tissue homogenates were assayed by enzyme-linked immunosorbent assay. In vitro, human neutrophils were isolated and treated with RPMI-1640 culture medium or that containing AGE-human serum albumin in the concentration of 0.315, 0.625, 1.250 mg/mL, and they were identified as normal control (NC) group, low concentration (L) group, moderate concentration (M) group, and high concentration (H) group. Cell viability in each group was determined by MTT colorimetric assay, and the reactive oxygen species (ROS) in cell was measured with 2', 7'-dichlorofluorescein-diacetate. Data were processed with t test.

RESULTSCompared with those of skin in control group, collagens of skin tissues in diabetes group atrophied and disorderly arranged. Inflammatory cells in wounds in diabetes group were dispersed, in which collagens arranged loosely and irregularly, as compared with those of wounds in control group. Expression levels of AGE and RAGE of skin in diabetes group were higher than those in control group. In diabetes and control groups, especially in diabetes group, the numbers of RAGE-positive cells in wound tissue were more than those in skin tissue. Large amount of inflammatory cells with positive expression of RAGE were observed in diabetes group. MDA level of skin and wound tissue in diabetes group was respectively (6.3 ± 1.0), (7.1 ± 2.4) nmol per milligram protein, which were obviously higher than those in control group [(2.9 ± 1.0), (3.6 ± 1.4) nmol per milligram protein, with t value respectively 8.017, 4.349, P < 0.05 or P < 0.01]. Cell viability and ROS levels in neutrophils were increased in L, M, and H groups [(59 ± 8)%, (77 ± 5)%, (67 ± 6)% and 1.67 ± 0.14, 2.13 ± 0.17, 3.48 ± 0.48] as compared with those in NC group [(34 ± 5)% and 0.58 ± 0.06, with t value respectively 7.195, 14.890, 11.130 and 20.195, 24.905, 16.864, P < 0.05 or P < 0.01].

CONCLUSIONSAbnormal oxidative stress in diabetic skin leads to an atypical origin of wound repair. AGE-RAGE effect is a critical mediator for oxidative stress in diabetic wound tissue during wound healing.

Aged ; Case-Control Studies ; Diabetes Mellitus, Type 2 ; metabolism ; pathology ; Female ; Glycation End Products, Advanced ; metabolism ; Humans ; Male ; Middle Aged ; Oxidative Stress ; Reactive Oxygen Species ; metabolism ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; metabolism ; Serum Albumin ; metabolism ; Serum Albumin, Human ; Skin ; metabolism ; pathology ; Wound Healing

OBJECTIVETo investigate molecular mechanism of tanshinone II A inducing differentiation and apoptosis in acute promyelocytic leukemia NB4 cells.

METHODNB4 cells were cultured in vitro and treated with tanshinone II A and observed cellular morphology, cell category and the cellular proliferation. DNA microarray technique was used to analyze the gene expression profiles of NB4 cells induced by tanshinone II A.

RESULT92.8% of NB4 cells treated with 0.5 mg x L(-1) tanshinone II A were induced into mature neutrophils, in which myetocytes and melamyetocytes were 27.0%, banded and segmented neutrophits 68.2%. Cell growth were inhibited. cDNA microarray showed the enormously expressed 183 genes including 23 differentiation associated genes, and other interrelated genes.

CONCLUSIONTanshinone II A inducing differentiation in NB4 cells may be via regulation of many kinds of genes, especially differentiation associated genes expression. This partially explained the molecular mechanism of tanshinone II A inducing differentiation.

Cell Differentiation ; drug effects ; Cell Line, Tumor ; Diterpenes, Abietane ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation, Leukemic ; drug effects ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; genetics ; metabolism ; Phenanthrenes ; pharmacology

Child, Preschool ; Echocardiography ; methods ; Humans ; Male ; Truncus Arteriosus, Persistent ; diagnostic imaging ; Ventricular Septum ; diagnostic imaging

OBJECTIVETo investigate the effects of aminoguanidine cream on the proliferation of keratinocytes (KC), content of advanced glycosylation end products (AGE) and oxidative stress in skin tissue of rats with diabetes.

METHODSStearic acid, liquid paraffin, vaseline, lanolin, isopropyl myristate fat, glycerol, 50 g/L alcohol paraben, aminoguanidine hydrochloride etc. were mixed in certain proportion to make aminoguanidine cream, and cream without aminoguanidine was used as matrix. The dorsal skin of normal rats were harvested and treated by aminoguanidine cream with dose of 5, 10 g/L, or 5 g/L together with 10 g/L azone. The transdermal effect was respectively measured at post treatment hour 2, 4, 7, 10, 12, 24. Thirty SD rats were divided into normal control (NC, n = 6), diabetes (D, n = 8), aminoguanidine cream-interfered (AI, n = 8), matrix cream-interfered groups (MI, n = 8) according to the random number table. Diabetes was reproduced by intraperitoneal injection of STZ (65 mg/kg) in rats of D, AI, and MI groups, and rats in NC group were injected with 0.05 mmol/L citrate buffer as control. One week later, dorsal skin of rats in AI and MI groups were respectively treated with 10 g/L aminoguanidine cream and matrix cream by external use for 4 weeks. AGE content was determined with fluorescence detection from skin collagen extract. KC cell cycle was detected by flow cytometry. Skin tissue specimens were obtained for determination of levels of superoxide dismutase (SOD), malondialdehyde (MDA), myeloperoxidase (MPO), and total antioxidant capacity. Data were processed with t test.

RESULTSTransdermal effect of aminoguanidine cream with dose of 10 g/L was better than that with 5 g/L or 5 g/L + 10 g/L azone cream. One rat was not induced successfully in MI group. Four weeks after model reproduction, 4 rats died in D group and 1 rat died in AI group. The AGE content in D group was obviously higher than that in NC group [(36.8 +/- 2.6), (24.6 +/- 2.7) U per milligram hydroxyproline, respectively, t = 7.2, P < 0.01], and that in AI group [(28.6 +/- 3.7) U per milligram hydroxyproline] was also lower as compared with that in D group (t = -3.9, P < 0.05). There was no significant difference in AGE content between MI [(32.2 +/- 5.2) U per milligram hydroxyproline] and D groups (t = 1.6, P > 0.05). The percentage of KC in S phase was obviously lower in D group than in NC group [(5.3 +/- 0.6)%, (7.6 +/- 0.9)%, respectively, t = 4.50, P < 0.01], while that in MI group [(9.2 +/- 1.5)%] was higher as compared with that in D group ( t = 4.90, P < 0.01). It was more higher in AI group than in D group on KC percentage in S and G2/M phase (with t value respectively 6.80, 3.17, P values all below 0.01). The oxidative stress indexes of skin tissue in D group were all higher than those in NC group, in which levels of MPO and SOD showed statistical difference (with t value respectively 4.4, 3.7, P values all below 0.05). The oxidative stress indexes were all lower in AI group than in D group, especially in SOD level (t = -1.4, P < 0.05). Levels of MAD, MPO in MI group were significantly lower than those in D group (with t value respectively 2.6, 2.9, P values all below 0.05).

CONCLUSIONSAminoguanidine cream can promote KC proliferation and appropriately reduce oxidative stress through inhibiting AGE formation to a certain extent in skin tissue of rats with diabetes. Signal use of matrix cream can also reduce oxidative stress in skin tissue of rats with diabetes.

Administration, Cutaneous ; Animals ; Cell Proliferation ; Diabetes Mellitus, Experimental ; metabolism ; pathology ; Glycation End Products, Advanced ; metabolism ; Guanidines ; administration & dosage ; pharmacology ; Keratinocytes ; drug effects ; Male ; Ointments ; administration & dosage ; pharmacology ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley ; Skin ; drug effects ; metabolism ; pathology

PURPOSE: To describe the therapeutic effect and possibility of the ultra-early surgery for poor-grade aneurysmal subarachnoid hemorrhage (Hunt-Hess grades IV - V). MATERIALS AND METHODS: Nine cases with intracranial aneurysms, demonstrated by computed tomographic angiography (CTA), were treated by ultra-early surgery under general anesthesia within 24 hours from subarachnoid hemorrhage (SAH), 5 cases were treated within 6 hours and 4 cases in 6 - 24 hours. Preoperative Hunt-Hess grade: 6 cases were IV and 3 cases were V. The clinical outcome was evaluated by Glasgow Outcome Scores (GOS). RESULTS: In operation, difficult dissection occurred in 5 cases (55.6%), and rupture of aneurysm occurred and temporary obstructions were performed in 4 cases (44.4%). After clipping of aneurysm, 2 cases underwent V-P shunt because of hydrocephalus, pulmonary infection occurred in 3 cases, hypothalamus reaction accompanied with upper gastrointestinal hemorrhage in 2 cases. The clinical outcome were favorable (GOS 4 - 5) in 4 cases (44.4%), dissatisfied (GOS 2 - 3) in 3 cases (33.3%), and dead (GOS 1) in 2 cases (22.2%) when patients departed from our hospital. CONCLUSION: The ultra-early surgery can avoid early rebleeding of intracranial aneurysm, therefore, should be considered in the treatment of Hunt-Hess grade IV-V intracranial aneurysms. The appliance of CTA can make it possible to use of ultra-early surgery and improve the therapeutic effect.
Adult ; Aged ; Cerebral Angiography ; Female ; Humans ; Intracranial Aneurysm/pathology/*surgery ; Male ; Middle Aged ; Subarachnoid Hemorrhage/pathology/*surgery