Primary biliary cirrhosis associated with minimal change disease.
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Biomedical subjects
Publications and source records attributed to Wei-Chou Lin.
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We performed multiphoton fluorescence (MF) and second-harmonic generation (SHG) imaging on human basal cell carcinoma samples. In the dermis, basal cell carcinomas can be identified by masses of autofluorescent cells with relatively large nuclei and marked peripheral palisading. In the normal dermis, SHG from dermal collagen contributes largely to the multiphoton signal. However, within the cancer stroma, SHG signals diminish and are replaced by autofluorescent signals, indicating that normal collagen structures responsible for SHG have been altered. To better delineate the cancer cells and cancer stroma from the normal dermis, a quantitative MF to SHG index is developed. We demonstrate that this index can be used to differentiate cancer cells and adjacent cancer stroma from the normal dermis. Our work shows that MF and SHG imaging can be an alternative for Mohs' surgery in the real-time guidance of the secure removal of basal cell carcinoma.
Renal cell carcinoma (RCC) is the most common malignancy in adult kidney, and accounts for 3% of malignancies worldwide with increasing incidence. Clear cell RCC (ccRCC) is the major type in RCC. Resection by surgery is the main treatment because the response of ccRCC to traditional therapies is very poor. To identify the tumor-associated genes for better understanding the molecular mechanism of ccRCC, the full-length enriched cDNA libraries of ccRCC and normal kidney tissues were constructed by the oligo-capping method. Nucleotide sequences of the cDNA libraries of ccRCC and normal kidney tissues were sequenced. From the sequence analysis of 19,425 and 12,400 clones of ccRCC and normal kidney tissues, 4356 and 3055 genes were identified, respectively. By comparing the gene-expression patterns of ccRCC and normal tissues, the up- or down-regulated genes were identified. Among these identified genes, the differential expression of annexin A2 and argininosuccinate synthetase genes were further confirmed by quantitative real-time PCR and Western blot analysis.
Keratoconjunctivitis sicca (KCS) is a common complication of graft-versus-host disease (GVHD), and may lead to corneal epithelial defect and melting. In contrast, recurrent corneal calcareous degeneration and perforation is rare. A 46-year-old woman developed chronic GVHD after bone marrow transplantation for aplastic anemia. Severe KCS with corneal melting and calcium deposits were noted in the left eye. Penetrating keratoplasty was performed because of corneal perforation, but poor re-epithelialization and calcium deposition recurred. Lamellar keratectomy and amniotic membrane transplantation (AMT) were performed, but acute calcareous degeneration developed with subsequent recurrence of corneal perforation. After regraft, AMT and tarsorrhaphy, the corneal graft remained clear for 3 months. However, breakdown of the corneal epithelium occurred 3 weeks after spontaneous separation of tarsorrhaphy. Six months later, corneal perforation recurred again along with exacerbation of GVHD. Regraft was performed, but the patient refused tarsorrhaphy and AMT. Poor re-epithelialization persisted after regraft. Corneal melting with impending corneal perforation ensued. Further corneal surgery was refused and the patient chose to undergo evisceration. This case demonstrates that the ocular complications of GVHD may be severe enough to lead to corneal perforation and calcareous degeneration that is recalcitrant to medical and surgical treatment.
Human immunodeficiency virus-associated nephropathy (HIVAN) is characterized by high-grade proteinuria and rapid progression to end-stage renal disease (ESRD). Despite the large numbers of HIV-infected cases in Asian countries, data on HIVAN in this area are limited. We report a 54-year-old Taiwanese man with HIVAN who presented with cytomegalovirus retinitis, renal insufficiency (serum creatinine, 3.8 mg/dL) and nephrotic range proteinuria with a daily protein loss of 10.8 g. Despite highly active antiretroviral therapy (HAART) for 31 months, renal failure developed requiring maintenance hemodialysis. Renal biopsy showed collapsing focal segmental glomerular sclerosis, podocyte proliferation and tubulointerstitial nephritis with mononuclear cell infiltration. These features were compatible with HIVAN. Although hemodialysis was instituted, he died 2 months later due to nosocomial pneumonia complicated with multiple organ failure. In summary, this case of HIVAN in a Taiwanese patient shows that the condition may progress to ESRD despite successful viral suppression with HAART.
BACKGROUND/PURPOSE: Pauci-immune glomerulonephritis (GN) is an important cause of crescentic GN, acute renal failure and mortality. However, data are limited on the clinical presentation and outcome in antineutrophil cytoplasmic antibody (ANCA) negative patients, especially in Asians. METHODS: This retrospective study analyzed medical records and pathology slides of patients who received renal biopsy between February 1998 and October 2004. Enzyme-linked immunosorbent assay was used routinely for ANCA testing in all patients. RESULTS: Among 637 patients with biopsy-proven GN included in this study, 88 (13.8%) had glomerular crescent formation. Among them, pauci-immune crescentic glomerulonephritis (PICGN) (42 patients, 47.2%) and lupus nephritis (25 patients, 28.4%) were the most common pathologic diagnoses. Lupus patients were younger (p = 0.028), while PICGN patients had more chronic lesions (p < 0.001), extensive glomerular crescents (p < 0.001), less severe proteinuria (p < 0.001) and poorer renal survival (p = 0.0017). Among the PICGN patients, 62.5% had a positive ANCA test, 80% had myeloperoxidase-ANCA and 20% had proteinase-3-ANCA. Subgroup analysis showed that ANCA negativity was associated with less crescent formation (p < 0.001) but more chronic glomerular lesions (p < 0.001) and a trend toward worse renal outcome (p = 0.055). CONCLUSION: This study illustrates the necessity for pathologic diagnosis of pauci-immune GN despite ANCA negativity. The poor prognosis associated with ANCA negativity in this study may be partly due to delayed diagnosis since these patients frequently lacked systemic involvement.
Primary liver lymphoma is a very rare disease and is frequently overlooked as a possible diagnosis. We report the case of an asymptomatic middle-aged man with chronic hepatitis C who developed primary liver lymphoma (PLL). A large solitary tumor in the left lobe of the liver was incidentally detected on routine ultrasound examination. Imaging studies showed mixed iso- and hypoechogenicity with hypoechoic rim, hypodense in the pre-contrast phase and thick wall enhancement in the post-contrast phase on computed tomographic study, hypointensity on T1WI, and hyperintensity of the central portion and slightly higher intensity in the peripheral wall on T2WI. These pictures were different from focal nodular hyperplasia, hepatocellular carcinoma, cholangiocarcinoma or metastases. Atypical hepatectomy was performed and the pathology of the hepatic tumor revealed non-Hodgkin's lymphoma. Systemic staging revealed no evidence of nodal or bone marrow involvement, so PLL was diagnosed. There was no tumor recurrence more than 4 years after operation and chemotherapy. PLL should be included in the differential diagnosis of solitary hepatic tumor in patients who are hepatitis C virus-positive, and who have atypical imaging and no known malignancy or elevated tumor marker levels.
PURPOSE: The purpose of this work was to demonstrate the use of the combined imaging modality of multiphoton autofluorescence and second-harmonic generation (SHG) microscopy in obtaining spectrally resolved morphologic features of the cornea, limbus, conjunctiva, and sclera in whole, ex vivo porcine eyes. METHODS: The 780-nm output of a femtosecond, titanium-sapphire laser was used to induce broadband autofluorescence (435-700 nm) and SHG (390 nm) from various regions of the surface of ex vivo porcine eyes. A water-immersion objective was used for convenient imaging of the curved surface of the eye. RESULTS: Multiphoton autofluorescence was useful in identifying cellular structures of the different domains of the ocular surface, and the SHG signal can be used to resolve collagen organization within the cornea stroma and sclera of ex vivo porcine eyes. CONCLUSIONS: Multiphoton autofluorescence and SHG microscopy have been demonstrated to be an effective technique for resolving, respectively, the cellular and collagen structures within the ocular surface of ex vivo porcine eyes. SHG imaging resolved the difference in structural orientations between corneal and sclera collagen fibers. Specifically, the corneal collagen is organized in a depth-dependent fashion, whereas the scleral collagen is randomly packed. Because this technique does not require histologic preparation procedures, it has the potential to be applied for in vivo studies with minimal disturbance to the eye.
PURPOSE: To demonstrate the application of multiphoton fluorescence (MF) and second harmonic generation (SHG) microscopy for ex vivo characterization of the structural alterations of human corneas due to keratoconus. METHODS: Buttons of keratoconic corneas derived from penetrating keratoplasty were sent for structural analysis with a custom-built multiphoton microscope. Fluorescence detected within the cytoplasm and the SHG signal obtained from collagen were used to demonstrate the morphologic changes in the corneal specimens. RESULTS: The fluorescent epithelial cells around the apical area were elongated and were aligned parallel to the adjacent collagen fibers. Parallel and centripetal distribution patterns of stromal collagen bundles were demonstrated at different depths within the keratoconic corneas. CONCLUSIONS: MF and SHG microscopy provides three-dimensional structural analysis of keratoconus ex vivo. It may provide important morphologic information for the investigation of the pathogenesis of keratoconus and may have potential in a clinical setting as an in vivo diagnostic and monitoring system for advancing keratoconus.
The photoaging process of facial skin is investigated by use of multiphoton fluorescence and second-harmonic generation (SHG) microscopy. We obtain the autofluorescence (AF) and SHG images of the superficial dermis from the facial skin of three patients aged 20, 40, and 70 years. The results show that areas of AF increase with age, whereas areas of SHG decrease with age. The results are consistent with the histological findings in which collagen is progressively replaced by elastic fibers. The AF and SHG changes in photoaging are quantified by a SHG to autofluorescence aging index of dermis (SAAID). Our results suggest that SAAID can be a good indicator of the severity of photoaging.
The thermal disruption of collagen I in rat tail tendon is investigated with second-harmonic generation (SHG) microscopy. We investigate its effects on SHG images and intensity in the temperature range 25 degrees-60 degrees C. We find that the SHG signal decreases rapidly starting at 45 degrees C. However, SHG imaging reveals that breakage of collagen fibers is not evident until 57 degrees C and worsens with increasing temperature. At 57 degrees C, structures of both molten and fibrous collagen exist, and the disruption of collagen appears to be complete at 60 degrees C. Our results suggest that, in addition to intensity measurement, SHG imaging is necessary for monitoring details of thermally induced changes in collagen structures in biomedical applications.
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AIMS: This retrospective study defined the clinical features and outcome of antineutrophil cytoplasmic antibody-associated glomerulonephritis in 18 seropositive Taiwanese patients (11 male, seven female; median age 64 years; range 21-82 years) with biopsy-proven pauci-immune necrotizing crescentic glomerulonephritis. RESULTS: Fourteen patients had a diagnosis of systemic vasculitis including 10 with microscopic polyangiitis and four with Wegener's granulomatosis; the remaining four had only glomerulonephritis. At onset, 100% of the systemic vasculitis patients had pulmonary lesions with or without haemoptysis, and 29% presented with seizure in the absence of a defined brain lesion. Median serum creatinine concentration was 362.4 micromol/L (range 61.9-857.5 micromol/L) and dialysis therapy was needed in six patients. During follow up (median 16.5 months; range 2-72 months), treatment included cyclophosphamide and corticosteroids (n = 8) or corticosteroids alone (n = 7). In some patients, treatment improved (n = 4) or stabilized (n = 4) renal function. But chronic dialysis was needed in the other 10 patients. Follow-up death occurred because of sepsis (n = 3) and haemorrhage (n = 2). Patient survival rates were 78% (1 year) and 72% (5 years). Renal survival rates were 56 and 39% at 1 and 5 years, respectively. Of the candidate clinical and pathological parameters, chronic glomerular lesions in renal biopsy were the only determinant of poor renal outcome (P = 0.006). CONCLUSION: Antineutrophil cytoplasmic antibody-associated glomerulonephritis should be considered in nephritic patients with extrarenal manifestations, especially pulmonary infiltrate, unexplained seizure, and fever of an unknown origin in Taiwanese patients. Renal biopsy should be performed before initiating immunosuppressive therapy because the most common cause of mortality was sepsis.
A cystic pancreatic tumour is rare in a child and a mature cystic teratoma of the pancreas is even rarer. This is the first demonstration of the CT appearance of such a tumour in a child. We present a 2-year-old boy who presented with a palpable abdominal mass. Abdominal CT revealed a huge cystic mass in the upper abdomen. Pathology disclosed a mature cystic teratoma originating from the pancreas.
We characterize the structural changes of porcine corneal structures from 25 to 90 degrees C using second harmonic generation (SHG) microscopy. Our results show that porcine stroma undergoes several distinct stages of structural changes between 25 and 90 degrees C. A decrease in SHG intensity from 30 to 45 degrees C and the existence of SHG intensity peaks at 53, 65, and 77 degrees C correlate to distinct structural alterations of the corneal stroma. At higher temperatures, the SHG intensity decreases and a baseline in SHG signal is reached at 90 degrees C. Our results demonstrate that SHG microscopy is a useful technique for obtaining qualitative and quantitative information of thermally treated corneal fibers without histological or labeling procedures. With additional developments, SHG imaging may be developed into an effective imaging technique for in vivo characterization of cornea structural changes.
Collagen shrinkage associated with denaturation from thermal treatment has a number of important clinical applications. However, individualized treatment is hindered by the lack of reliable noninvasive methods to monitor the process of collagen denaturation. We investigate the serial changes of collagen denaturation from thermal treatment of rat tail tendons at 58 degrees C by use of second harmonic generation (SHG) microscopy. We find that rat tail tendon shrinks progressively from 0 to 9 min of thermal treatment, and remains unchanged in length upon further thermal treatment. The SHG intensity also decreases from 0 to 9 min of thermal treatment and becomes barely detectable from further thermal treatment. Collagen shrinkage and the SHG intensity are well correlated in a linear model. In addition, SHG imaging reveals a tiger-tail-like pattern of collagen denaturation. The bands of denatured collagen progressively widen from increased thermal treatment and completely replace the adjacent bands of normal collagen after 9 min of thermal treatment. Our results show that collagen denaturation in rat tail tendon from thermal treatment is inhomogeneous, and that SHG intensity can be used to predict the degree of thermally induced collagen shrinkage. With additional development, this approach has the potential to be used in biomedical applications.