Molecular genetic analysis of a Chinese patient with Fabry disease.
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Adolescent↗
Biomedical subjects
F M Lai
Publications and source records attributed to F M Lai.
Oxytocin and vasopressin constrict rat isolated uterine resistance arteries by activating vasopressin V1A receptors.
Both oxytocin and vasopressin cause potent and long-lasting vasoconstriction of uterine arteries from several species, including humans, and the resulting tissue ischemia is thought to be involved in the pathogenesis of primary dysmenorrhea. We have studied the effects of oxytocin and vasopressin in isolated resistance arteries (diameter, 90-120 microm) from non-pregnant rat uteri using two potent and selective receptor antagonists, SR 49059, a selective vasopressin V1A antagonist, and atosiban, a selective oxytocin antagonist. Uterine arteries with intact endothelium were mounted in a microvessel chamber, and pressurized to 75 mm Hg to allow the development of myogenic tone. Both vasopressin and oxytocin elicited a concentration-dependent vasoconstriction with a similar maximum effect (i.e., total vessel occlusion). The EC50 was 0.44 +/- 0.02 and 25 +/- 3.1 nM for vasopressin and oxytocin, respectively. Thus, vasopressin was 57-fold more potent than oxytocin. Schild analysis indicated that SR 49059 yielded a similar pA2 value against vasopressin-induced (pA2 = 8.96 +/- 0.60) or oxytocin-induced (pA2 = 9.06 +/- 0.23) contractions, suggesting that both agonists activated the vasopressin V1A receptor. In addition, atosiban (10(-7) M), a selective antagonist of the oxytocin receptor in the rat, did not antagonize the effect of vasopressin and oxytocin, showing that the oxytocin receptor is not involved in the response. In conclusion, these results suggest that V1A receptor stimulation is responsible for the vasoconstricting effects of both vasopressin and oxytocin in small diameter resistance arteries from the rat uterus.
Animals↗
Acute renal failure in a patient with Rosai-Dorfman disease.
Acute renal failure developed in a 57-year-old woman who had Rosai-Dorfman disease diagnosed 1 year previously on a cervical lymph node. Organ imaging showed diffuse masses infiltrating both kidneys. The renal biopsy showed a lymphoplasmacytic and histiocytic process extensively replacing the parenchyma, which is in keeping with Rosai-Dorfman disease of the kidneys. However, the typical lymphophagocytic cells were lacking. This case illustrates that diagnosis of Rosai-Dorfman disease in renal biopsy can be very difficult, requiring both exclusion of many benign and malignant lesions and a high index of suspicion for this condition. In particular, lymphoma was excluded based on the mixed polyclonal composition of inflammatory cells and the absence of atypical lymphoid proliferation. The renal function partially recovered after a course of therapy combining VP-16 (etoposide) and dexamethasone and remained stable over 4-year follow-up. This report emphasizes the importance of early diagnosis and intervention to safeguard renal function in extensive Rosai-Dorfman disease.
Acute Kidney Injury↗
Coexistence of Kaposi's sarcoma and tuberculosis in a renal transplant recipient.
BACKGROUND: We describe a case of Kaposi's sarcoma that developed in a renal transplant recipient as early as 5 months after the transplant. METHOD: The Kaposi's sarcoma evolved in an aggressive manner, involving the oral mucosa, the cervical and mediastinal lymph nodes, the gastrointestinal tract, and possibly the lung. Histological features of tuberculosis were also detected incidentally on an excisional biopsy of the lymph node. The patient was given 12 months of antituberculous chemotherapy. At the same time, immunosuppression was gradually tapered over a 2- to 3-week period. RESULTS: Despite the aggressive nature of the disease, the Kaposi's sarcoma regressed completely without the institution of chemotherapy. The patient remained disease-free after a follow-up period of 30 months. The kidney allograft, however, was rejected and the patient required dialysis again. CONCLUSION: Although lymphadenopathy is a well-recognized feature in organ transplant recipients who develop Kaposi's sarcoma, one has to watch out for other coexisting diseases, such as tuberculosis, lymphoma, and cytomegalovirus infection.
Adult↗
Characterization of muscarinic receptors mediating the contraction of the urinary detrusor muscle in cynomolgus monkeys and guinea pigs.
We have characterized in vitro the muscarinic receptors mediating the contraction of the detrusor muscle in Cynomolgus monkeys and guinea pigs using carbachol as the agonist and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, M3-selective), methoctramine (M2-selective) and pirenzepine (M1-selective) as the antagonists. Carbachol induced a concentration-dependent contraction of the detrusor muscle of monkey and guinea pig yielding similar pD2 values of 6.67+/-0.03 (n=50) and 6.77+/-0.06 (n=36), respectively. In the detrusor muscle of Cynomolgus monkey, all antagonists produced a concentration-dependent inhibition of carbachol-induced contractions, without decreasing the maximal response. Schild plot analysis yielded slopes not different from unity for all antagonists. The order of antagonist potency was: 4-DAMP (pA2=8.96)>pirenzepine (pA2=6.66)>methoctramine (pA2=6.03), suggesting that M3 receptors have a dominant role in mediating detrusor contraction. In the detrusor muscle of the guinea pig, 4-DAMP and pirenzepine, but not methoctramine, produced a concentration-dependent inhibition of the carbachol-induced contractions, without decreasing the maximal response. Schild plot analysis yielded a slope not different from unity for 4-DAMP and pirenzepine. 4-DAMP (pA2=9.07) had a higher potency than pirenzepine (pA2=6.66), a finding consistent with previously published data. The present study shows that in Cynomolgus monkey stimulation of the M3 subtype is dominant in mediating detrusor contraction upon carbachol stimulation.
Animals↗
Effective treatment of high-grade lymphoproliferative disorder after renal transplantation using autologous lymphocyte activated killer cell therapy.
Posttransplantation lymphoproliferative disorders (PTLD) is not uncommon and can occur in 2% to 5% of solid organ recipients on immunosuppression. Epstein-Barr virus (EBV) infection or reactivation and intensive anti-T lymphocyte treatment are important pathogenetic factors for a large proportion of these disorders. Nonclonal lesions with polymorphous histology have a potential for regressing when the immunosuppressants are reduced or stopped. Clonal tumors with a monomorphous histology carry a poor prognosis, and the mortality rate for monoclonal lymphoma has been reported as high as 80%. We report a renal transplant recipient who developed high-grade monoclonal lymphoma only 4 months after a live-donor transplantation. The tumor was EBV positive. Reduction of immunosuppressants resulted in minimal regression of the tumor. The patient was treated with adoptive immunotherapy using ex vivo generation of autologous lymphocyte activated killer (LAK) cells. She had leukapheresis, and autologous peripheral blood mononuclear cells were obtained and cultured in interleukin-2 (IL-2)-rich medium for 9 to 10 days. The IL-2-activated LAK cells were reinfused into the patient without any systemic administration of IL-2. The patient experienced no side effects during the infusion. There was no rejection episode, and the renal function of the patient remained stable after treatment. Computed tomography scan performed 2 months after the infusion showed marked regression of the lesions in the liver and spleen. Five months later, magnetic resonance imaging showed complete resolution of the tumor lesions. Ultrasonography 13 months after the LAK cell infusion showed no lesion. The allograft function was not affected after treatment. Adoptive immunotherapy using IL-2-activated autologous LAK cells was effective in treating this renal transplant patient with EBV-positive high-grade lymphoma. The patient's kidney allograft functioned well without any rejection.
Adult↗
Long-term treatment of lupus nephritis with cyclosporin A.
We evaluated the efficacy and safety of long-term treatment with cyclosporin A (CSA) in type IV lupus nephritis. Seventeen patients with biopsy-proven WHO type IV lupus nephritis were enrolled in a prospective, open study. Twelve of the 17 completed 48 months of treatment with CSA and prednisolone. Three patients required the addition of azathioprine, at 12, 38 and 47 months, respectively, for cutaneous disease flare with refractory rashes. One patient was lost to follow-up at 40 months. The mean +/- SD duration of treatment was 43.2 +/- 10.1 months (range 15.7-48 months). A significant reduction of proteinuria and a significant rise in serum albumin were noted 1 month after initiation of treatment. Improvement was maintained throughout the study except for three patients who relapsed with recurrence of nephrotic syndrome. There were no significant changes in serum creatinine level or creatinine clearances throughout the study. Repeat renal biopsy at 12 months following treatment with CSA showed histological improvement, with WHO type II changes in all 17 patients accompanying significant reduction in activity indices. Patients with baseline haemoglobin (Hgb) levels < 12 g/dl showed significant improvement. Serum C3 and C4 levels were not changed significantly. Corticosteroid-sparing effects were noted. Side-effects included hypertension, gum hypertrophy and mild hirsuitism, but were not serious. Combination therapy using CSA and prednisone is effective and safe for long-term treatment in lupus patients with WHO type IV nephritis.
Adult↗
Gene expression of the renin-angiotensin system in human kidney.
BACKGROUND: Immunocytochemical studies have revealed that all components of the renin-angiotensin system are widely distributed in human tissues yet the information on the gene expression of the renin-angiotensin system in various types of cell remains scarce. OBJECTIVE: We explored the presence of a local renin-angiotensin system in human kidney. METHODS: We sought to determine the presence of messenger RNA (mRNA) encoding for renin, angiotensinogen, and angiotensin converting enzyme (ACE) in cultured human glomerular cells and human umbilical vein endothelial cells using a two-step polymerase chain reaction. The gene expression of the renin-angiotensin system in normal human kidney and in diseased kidney was studied by in-situ hybridization using synthetic oligonucleotides. RESULTS: By using a two-step polymerase chain reaction, renin, angiotensinogen, and ACE mRNA were found in cultured mesangial and epithelial cells but only ACE mRNA was present in human umbilical vein endothelial cells. Renin mRNA was detected in juxtaglomerular granular cells and also in glomerular and tubular epithelia in normal kidney by in-situ hybridization. A similar tubular, but not mesangial, distribution was found with angiotensinogen and ACE mRNA. In contrast, stronger signals for renin, angiotensinogen and ACE mRNA were detected in mesangial and epithelial cells of kidney tissues from hypertensive patients and from patients with renal pathology characterized by mesangial proliferation (immunoglobulin A nephropathy, diabetes mellitus, or lupus nephritis). CONCLUSIONS: That gene expression of the renin-angiotensin system occurs in resident glomerular cells supports the hypothesis that there is a local renin-angiotensin system in human kidney. Our findings support the previous speculation that the renin-angiotensin system could be a local factor involved in the progression of chronic renal failure and consequent development of hypertension.
Angiotensinogen↗
Down syndrome screening in Singapore--the effectiveness of a second trimester serum screening policy modelled on 29,360 pregnancies in KK Women's and Children's Hospital.
AIM OF STUDY: To assess the effectiveness of a proposed second trimester Down syndrome serum screening policy in Singapore. METHOD: Auditing the effectiveness of an age-only policy and comparing it against a serum screening policy modelled on the same maternal population of KK Women's and Children's Hospital in 1994 and 1995. RESULTS: KK Women's and Children's Hospital's (KKH) maternal age distribution is similar to the national age distribution of mothers. Sixteen percent (16.7%) of mothers in KKH, in 1994 and 1995, were 35 years or older at delivery. Based on our hospital birth defect registry, 66% (35/53) of Down Syndrome pregnancies occurred in mothers who were 35 years or older at delivery and 43% (23/53) in the oldest 6.5% of mothers (38 years or older at delivery). Using various models on KKH's population structure to estimate the expected number of Down Syndrome livebirths expected, 52%-55% and 34%-36% of Down Syndrome livebirths were expected to occur in the oldest 16.7% and 6.5% of mothers respectively. These simulated figures are much lower than the figures from the data and needs further study, assuming that the Western Down Syndrome risk model to be applicable to our population. The overall uptake of amniocentesis irrespective of gestational age at booking was 28%. In mothers who were 35 years or older at delivery and booked before 22 weeks gestation, the uptake rate of amniocentesis was 49%. There was a substantial difference in the uptake rate when the counselling was done by trained counsellers compared to those who were not. CONCLUSION: We would expect that for a fixed amniocentesis rate of 6.5% and 16.7%, serum screening would be able to detect 71% and 85% respectively of the Down syndrome pregnancies. This is more efficient than figures published from Western populations as our patients are older.
Amniocentesis↗
Acute renal failure and proximal tubule lesions after trichosanthin injection in rats.
The structural basis of the recently recognized renal impairment after infusion of trichosanthin (TCS), a type I ribosome inactivating protein, is uncertain, but functionally it appears to be related to a lesion in the renal tubules. In this study, renal dysfunction in experimental rats was induced by a single dose of TCS. Creatinine clearance and tubular proteinuria were used to assess renal function. Light microscopy and ultrastructure of the kidneys were examined and apoptosis in proximal tubules was evaluated by the in situ TdT-mediated nick end labeling technique. TCS-treated rats demonstrated a significant dose-dependent decrease in creatinine clearance together with a mild degree of low-molecular-weight proteinuria. The proximal convoluted tubule was the site of lesions showing individual tubular cell death, which was more abundant in rats receiving high doses of TCS. Apoptotic cell death, together with heterophagosomes and large residual bodies, was observed. DNA fragmentation was confirmed by the in situ technique. There was also a dose-dependent density of apoptotic cells. Other portions of the nephron were spared, and it was not accompanied by any inflammatory infiltrate. In conclusion, these findings are consistent with TCS-induced proximal tubular toxicity resulting in reduction of glomerular filtration rate and tubular proteinuria. The extent of injury is dosage dependent. Both necrotic cell death and apoptosis participated in the loss of cells from the proximal tubules. Such toxicity may be mediated through intracellular events induced by trichosanthin.
Acute Kidney Injury↗
Caroli's disease: functional diagnosis using 99mTc diethyl-iminodiacetic acid (IDA) hepatobiliary scintigraphy.
A case of Caroli's disease is presented and the findings of various imaging modalities are discussed with emphasis on the role of Technetium 99mTc diethyl-iminodiacetic acid scan in reaching the final diagnosis. The 'beaded' appearance of the dilated intrahepatic ducts seen in this scan is believed to be pathognomonic for this condition.
Bile Ducts, Intrahepatic↗
The role of 67gallium scintigraphy and high resolution computed tomography as predictors of disease activity in sputum smear-negative pulmonary tuberculosis.
SETTING: University Hospital, Kuala Lumpur, Malaysia. OBJECTIVE: To determine whether 67Gallium (Ga) scintigraphy and high resolution computed tomography (HRCT) of the lung improve the diagnostic accuracy of sputum smear-negative active pulmonary tuberculosis. DESIGN: Patients suspected of having active pulmonary tuberculosis but who were sputum smear-negative underwent 67Ga scintigraphic and HRCT scanning of the lung. Results of these scans were correlated with results of bacteriology and histopathology as well as clinical data on follow-up. RESULTS: Although none of the patients was culture-positive for Mycobacterium tuberculosis, 14 were considered to have active disease either because of positive direct smears of respiratory tract specimens other than sputum, positive histopathology, or clinical and radiological improvement following antituberculosis chemotherapy. A positive 67Ga scan had a sensitivity of 100% and a specificity of 83% for active pulmonary tuberculosis. Of the HRCT findings, the presence of centrilobular lesions had a 93% sensitivity and 100% specificity in determining disease activity in this group of patients. CONCLUSION: Both 67Ga scintigraphic and HRCT scans are helpful in determining disease activity in sputum smear-negative pulmonary tuberculosis.
Female↗
Respiratory symptoms and pulmonary function in mill workers exposed to wood dust.
This study surveyed wood dust exposure levels and pulmonary hazards among wood mill workers. Dust concentrations as measured by six-stage cascade impactors were high in work areas of grinding and screening. Total dust concentrations for these dusty activities ranged from 4.4 to 22.4 mg/m3, and the respirable proportions were between 2.4% and 50.2%. The dust level in the sawing work was 2.9 mg/m3. Although symptoms of cough and phlegm were higher in smoking workers than in nonsmoking workers, the prevalence of respiratory symptoms in the exposed workers was not significantly higher than in the controls. However, the incidence of symptoms such as chronic phlegm and chronic bronchitis in the nonsmoking high-exposure workers was significantly higher than in nonsmoking controls. The mean values of MMF, PEFR, and FEF25% were significantly lower in the exposed workers than in controls for both smokers and nonsmokers. The pulmonary function deficits, with the exception of FEV1.0/FVC, also showed a significant trend with increasing levels of wood dusts exposure classified by job titles for both smokers and nonsmokers. After adjustment for age, sex, height, and smoking status, all parameters of pulmonary function were significantly lower in exposed workers than in controls and showed a declining trend with increasing exposure levels classified by job titles. These results indicate that high level of wood dust exposure in the wood mill industries may lead to pulmonary hazards. Engineering control and industrial hygiene are mandatory for dusty activities.
Adult↗
Neutrophil attractant protein-1 interleukin 8 and its autoantibodies in IgA nephropathy.
Human neutrophil attractant protein-1/interleukin 8 (IL-8) has been shown to activate neutrophils to degranulate in vitro and to be a potent chemotactic agonist for neutrophils and lymphocytes in vitro and in vivo. There is accumulating evidence that neutrophils are involved in inflammatory injury in IgA nephropathy (IgAN). We studied the serum levels of IL-8 and its autoantibodies of the IgA or IgG class in 36 patients with IgAN in comparison with 31 healthy controls and 26 patients with other primary glomerulonephritides (CGN). Interleukin 8 was more frequently detected in sera of patients with IgAN and their serum levels were significantly higher than those of healthy controls. The free IL-8 autoantibodies of the IgA, but not IgG class, were more frequently detected in patients with IgAN and their serum levels were significantly elevated compared with both groups of controls. The complexed IL-8 autoantibodies of either class were not different among the three groups of subjects. Again the ratio of free to complexed IL-8 autoantibodies of the IgA class was raised in patients with IgAN. Histologic examination revealed increased polymorphs and monocyte/macrophage infiltration in IgAN compared with other glomerulonephritides. When the serum levels of IL-8 and IL-8 autoantibodies were compared between IgAN patients with milder pathology and those with more severe pathology, the latter group had significantly higher serum levels of free and complexed IL-8 autoantibodies of the IgA class. These observations suggest a possible role for IL-8 and its autoantibodies of the IgA class in the inflammatory process of IgAN. These autoantibodies may provide a clinically useful marker for the diagnosis of disease severity.
Adult↗
Respiratory symptoms and pulmonary function among wood dust-exposed joss stick workers.
Health hazards associated with wood dust exposure have been investigated in various industries. This study surveyed wood dust exposure levels and pulmonary effects among joss stick workers. Greater dust concentrations, as measured by six-stage cascade impactors, were observed in work areas where joss sticks were produced and incense was mixed than in other work areas. Total dust concentrations for these two high dust activities ranged from 9.9 to 42.7 mg/m3, and respirable proportions were between 2.0% and 54.6%. Higher dust levels were observed for dry joss stick production methods than for wet production methods. Dust levels for all other performance areas were lower than the permissible exposure level of 10 mg/m3. Although symptoms of cough and phlegm were higher in smoking workers than in nonsmoking workers, the prevalence of respiratory symptoms for exposed workers was not significantly higher than for the controls. The prevalence of pulmonary function deficits and the values of FEF25% and FEF75% in the exposed workers were significantly worse than those in the controls. But no difference was found between the male controls and the male exposed workers, the high-exposure group. Respiratory symptoms and pulmonary function also did not show a dose-response trend with the exposure levels estimated by correlation with worker job titles and duration of employment. No suspected case of pneumoconiosis was found from the chest radiographs. These results suggest that wood dust exposure in the joss stick industries might not lead to significant pulmonary damage.
Adult↗
Alport's syndrome in monozygotic twins.
Identical twins presented at the same time with renal failure. They also recalled a simultaneous history of "nephritis" as early as the age of 6 years. Renal biopsies revealed variably thickened glomerular basement membranes with the lamellation and splitting characteristic of Alport's syndrome. Bilateral sensorineural deafness was demonstrated in both twins on audiometric testing. A positive family history in the mother and one elder sister confirmed the diagnosis of Alport's syndrome. This is the first reported case of Alport's syndrome occurring in monozygotic twins.
Adult↗
Detection of hepatitis B virus DNA and RNA in kidneys of HBV related glomerulonephritis.
Glomerular deposition of hepatitis B virus (HBV) antigens are observed in chronic HBsAg carriers with different glomerulonephritides yet the etiologic role of HBV remains uncertain. We examined the paraffin section of kidney biopsies from 40 chronic HBsAg carriers with membranous nephropathy (MGN), mesangiocapillary glomerulonephritis (MCGN) or IgA nephropathy (IgAN) for HBV DNA and HBV RNA using in situ hybridization (ISH). Glomerular HBV antigens were present in all biopsies by immunofluorescence. HBsAg or HBcAg mRNA was also studied in RNA extracted from frozen renal tissue using a two-step polymerase chain reaction (PCR) following reverse transcription (RT). HBcAg DNA was not easily detected with ISH alone, but was readily found in 31 biopsies (78%) following PCR. HBV DNA was detected mainly in the cytoplasm of proximal tubular epithelia but not in glomerular cells. HBsAg and/or HBcAg mRNA were detected by RT-PCR in extracted RNA from 13 biopsies (33%). The PCR findings were further confirmed by (a) Southern blot hybridization using a cloned HBV probe and (b) absence of PCR product following treating RNA with RNase or omitting the RT. It is plausible that HBV DNA in renal tubules represents endocytosis of HBV DNA in the urinary filtrate and the HBV RNA extracted from kidney biopsies could derive from infiltrating cells bearing HBV RNA. Hence, ISH with specific HBV core gene RNA probe was performed subsequently. HBcAg RNA, localized in the nuclei and cytoplasm of glomerular and tubular cells, was detected in 56%, 20%, and 36% of renal biopsies in chronic HBsAg carriers with MGN, MCGN, and IgAN, respectively. Our findings indicate the presence of viral transcription in glomerular cells and renal tubular epithelia, supporting an etiological role of HBV in some chronic HBsAg carriers who develop coexisting glomerulonephritides.
Adolescent↗
Increased release of von Willebrand factor antigen from endothelial cells by anti-DNA autoantibodies.
OBJECTIVE: To determine whether antibodies to double stranded DNA (anti-dsDNA) have a pathogenic role in systemic lupus erythematosus (SLE). METHODS: IgG was purified from 17 patients with SLE (median anti-dsDNA titre 1212 IU/ml) and nine healthy controls (median titre 40 IU/ml). Anti-dsDNA depleted polyclonal IgG (median anti-dsDNA titre 17 IU/ml) was also prepared from sera of the 17 patients by affinity chromatography on a DNA cellulose column. Binding to antiendothelial cell antibodies (AECA) and expression of von Willebrand factor (VWF) antigen by cultured human umbilical vein endothelial cells (HUVECs) were studied by flow cytometry. RESULTS: The percentage of HUVECs binding to AECA or expressing VWF was greater for cells incubated with IgG from patients with SLE than for cells incubated with control IgG, though values did not reach statistical significance; nevertheless, HUVECs incubated with IgG from patients expressed a greater mean fluorescence intensity with AECA (p = 0.0001) and greater VWF expression (p = 0.019). Both the fluorescence intensity and percentage of HUVECs binding to AECA or expressing VWF were significantly greater in HUVEC incubated with IgG containing anti-dsDNA than in those incubated with anti-dsDNA depleted IgG. The concentration of VWF in the supernatant was significantly increased in HUVECs incubated with IgG containing anti-dsDNA compared with control IgG or anti-dsDNA depleted IgG. Pretreatment of HUVECs with native DNA before incubation with IgG from lupus patients did not increase binding to AECA, or expression or release of VWF. CONCLUSIONS: Our study provides in vitro evidence that antibodies to DNA have a pathogenic role in the induction of inflammatory injury of the vascular endothelium in SLE.
Adult↗