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Biomedical subjects

W J Lee

Publications and source records attributed to W J Lee.

At least 19 recordsLinked to original sources

A genome-wide association study of methamphetamine use among people with HIV.

BACKGROUND: Amphetamine-like stimulants are the most used psychostimulants in the world; methamphetamine use is the most prevalent in people with HIV. Prolonged methamphetamine use can cause lasting damage to the heart, gut, and brain, as well as auditory hallucinations and paranoid thinking. However, relatively little is known about methamphetamine use and its genetic contributors. METHODS: Using genetic information from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort, we conducted a multi-ancestry genome-wide association study (GWAS) of methamphetamine use among people with HIV (n&#x2009;=&#x2009;1,196 reported ever use, n&#x2009;=&#x2009;4,750 reported never use). RESULTS: No single nucleotide polymorphism was statistically associated with methamphetamine use at the genome-wide level (p&#x2009;<&#x2009;5 * 10-8) in our study. Further, we did not replicate previously suggested genetic variants from other studies (all p&#x2009;>&#x2009;0.05 in our analysis). DISCUSSION: Our study suggests that there is no single strong genetic contributor to lifetime use of methamphetamine in people with HIV enrolled in CNICS. Larger studies with more refined outcome assessment are warranted to further understand the contribution of genetics to methamphetamine use and use disorder. Investigation into social and environmental contributors to methamphetamine use are similarly necessary.

Humans

Expression of calpain II gene in human hematopoietic system cells infected with human T-cell leukemia virus type I.

We examined the distribution of calpains I and II in human hematopoietic system cell lines by Western and Northern blot analyses and enzyme activity assay. Expression of calpain I, a low Ca(2+)-requiring cysteine protease, was observed in all human T-cell lines tested. By contrast, expression of calpain II, a high Ca(2+)-requiring form, in human T-cells was closely correlated with human T-cell leukemia virus type I (HTLV-I) infection, which is known to result in the expression of adult T-cell leukemia-associated antigens, interleukin-2 (IL-2) receptor alpha, and Ca(2+)-dependent cell proliferation. Specific expression of calpain II in HTLV-I-infected cells occurred at the mRNA level. Furthermore, expression of calpain II in human natural killer-like cells was augmented by HTLV-I pX gene transfection. In HTLV-I-infected cells, the trans-acting transcriptional activation of the long terminal repeat and control elements for the IL-2 receptor alpha, c-fos, and granulocyte-macrophage colony-stimulating factor genes by the Tax from the pX gene is already known. Our results suggest that the similar trans-activation occurs to the calpain II gene in HTLV-I-infected hematopoietic system cells.

Blotting, Western

Molecular diversity in amino-terminal domains of human calpastatin by exon skipping.

Calpastatin, a specific inhibitor of calpain, consists of a unique N-terminal domain (domain L) and four repetitive calpain-inhibition domains (domains 1-4). Calpastatin cDNA of human was reported to have two deletions in domains L and 1, as compared with that of pig and rabbit. We isolated human calpastatin genomic DNA clones, and the sequence analysis revealed seven exons for domain L and five exons for domain 1. Those deletions in the human cDNA were retained in its genomic DNA as exons 3 and 11. By the reverse transcription polymerase chain reaction method, three calpastatin cDNAs, full-length domains L and 1, and two natural mutants with deletions in either exon 3 or in both exons 3 and 5, were cloned from human fibroblast WI-38 cell line mRNA. Domain L was found to be rich in basic amino acid residues, especially for exon 3, and its N-terminal half was highly conserved among species. The isoelectric points (pI) of domain L and domains 1-4 were calculated to be 10.27 and 4.26-4.90, respectively. Moreover, human tissues and cell lines displayed different patterns of reverse transcription polymerase chain reaction products in agarose gel electrophoresis. Therefore, alternative splicing is most likely the cause for the molecular diversity, and the multiple isoforms are implicated for specific physiological roles.

Base Sequence

Multiple forms of rat calpastatin cDNA in the coding region of functionally unknown amino-terminal domain.

Partial mouse and rat calpastatin cDNAs containing functionally unknown amino-terminal regions were cloned by the polymerase chain reaction (PCR) method. Two types of clones were obtained for the rat calpastatin; one had a sequence similar to mouse and human calpastatins, while the other had a deletion of 38 amino acid residues in this region. Both types of the rat sequence differed from the previously reported rat calpastatin which had additional deletions. The occurrence of multiple forms of calpastatin suggests alternative splicing in the functionally unknown domain.

Amino Acid Sequence

Characterization of chemotherapy mobilized peripheral blood progenitor cells for use in autologous stem cell transplantation.

Twenty patients were treated with chemotherapy to mobilize progenitors into the blood. Peripheral blood stem cells were quantitated in peripheral blood or leukapheresis products using colony assays and flow cytometric measurement of CD34+ cells. In four patients where complete sets of serial samples were obtained, the appearance of CD34+ cells preceded the increase in CFU-GM by 24-48 h. Peak levels of CD34+ cells ranged from 0.6-5% and coincided with the peak increase in CFU-GM. Mobilized CD34+ cells contained subsets expressing CD33, CD13, CD45RA, CD38, HLA-DR, CD61 and CD41. Subsets of CD34+ cells expressing CD33, CD13, or CD45RA represent committed myeloid progenitors. In contrast to bone marrow CD34+ cells, few mobilized CD34+ cells expressed CD71, CD7, CD19 or CD10. Prompt engraftment of granulocytes greater than 500 x 10(6)/l at a median of 13 days and platelets greater than 50 x 10(9)/l at a median of 15 days was observed in patients reconstituted with mobilized cells. These data indicate that CD34+ cells mobilized during recovery from chemotherapy are predominantly myeloid in phenotype and contain few actively proliferating cells or cells with lymphoid phenotypes.

Antigens, CD

Surgery in cholangitis: bacteriology and choice of antibiotic.

Owing the frequent occurrence of intrahepatic stones in orientals, cholangitis presents a real problem. Surgery and antimicrobial drug therapy are the main forms of treatment. A retrospective study of choledochotomy, including biliary tract surgery, performed between July 1987 and June 1990, was conducted. Cases with negative common duct exploration during cholecystectomy were excluded. Among 186 cases, 128 (68%) had positive bile growth, which was defined as cholangitis. Sepsis-related complications occurred in 51 patients (27.4%), including 3 surgical deaths, 30 wound infections, and 18 others. The complication rate was higher in the cholangitis group than in the negative group (37.5% vs. 5.2%). However, if peri-operative antibiotics were effective against the cultured bacteria species, the complication rate was 16.9%; if not, the complication rate was 85.3%. For the different-generation cephalosporins used in the peri-operative period, the complication rates were 32.2%, 20.8%, and 27.6% each for 1st, 2nd, and 3rd generation cephalosporins, with no statistically significant differences. In microbiological study, polymicrobial infection was the rule. On average, 2.3 species were grown from each specimen. Enterococcus proved the most important species with a 54% culture rate. E. coli and Pseudomonas were important gram-negative bacilli, with culture rates of 46.1% and 39.1%, respectively. Anaerobic species were cultured in 12.3% of the patients. For good coverage of cholangitis prior to operation, the proper antibiotic should have potency against gram-positive Enterococcus, gram-negative bacilli, especially Pseudomonas and E. coli, and anaerobic species, especially Bacteroides.

Adult

Immunohistochemical and biochemical demonstration of calcium-dependent cysteine proteinase (calpain) in calcifying cartilage of rats.

Calpain is a Ca2(+)-dependent cysteine proteinase that has neutral pH optima. There are two classes of calpains that differ in their optimal calcium ion concentration for enzymatic activity. Calpain I requires a low concentration of Ca2+ for activation, and calpain II requires a much higher Ca2+ concentration. This report describes the immunohistochemical and biochemical demonstration of calpain II in calcifying cartilage in rats and also the degradation of the cartilage proteoglycan subunit by calpain II. Immunoperoxidase (peroxidase-antiperoxidase) staining of the frozen sections of the knee joint from 3-day-old and 6-day-old Wistar rats, using polyclonal antibodies against the respective heavy subunits of calpains I and II, showed positive staining only with the anti-calpain II antibody in the hypertrophic chondrocytes and surrounding cartilaginous matrix of the growth cartilage. Diethylaminoethyl-cellulose chromatography of the cartilaginous extract from 3-day-old rats showed a peak of caseinolytic activity attributable to calpain as well as an inhibitory peak of calpastatin, a specific inhibitor protein of calpains. Immunoblotting using the anti-calpain II antibody of the calpain peak demonstrated identity with the heavy subunit of calpain II (80 kDa). Proteoglycan-degrading activity of calpain was assessed using porcine kidney calpain II and the porcine articular cartilage proteoglycan subunit. After incubation in the presence of Ca2+, degradation of proteoglycan was demonstrated by the change of the elution position on Sepharose-2B chromatography. It is possible that calpain functions as one of the proteoglycan-degrading proteolytic enzymes of growth cartilage. Intracellular localization of calpain in hypertrophic chondrocytes also suggests a role in the hypertrophic process of the chondrocyte in growth cartilage.

Animals

Congenital broncho-oesophageal fistula in the adult.

Five patients with congenital broncho-oesophageal fistula confirmed by fistulectomy are presented. Clinical symptoms were chronic or recurrent pulmonary infection, and three patients experienced coughing after swallowing. Pre-operative oesophagograms demonstrated broncho-oesophageal fistulas in all five patients. The fistulous communications were from the lower oesophagus to segmental bronchi of the lower lobe and to the left main bronchus. The fistulas showed smooth marginated serpentine margins with areas of internal trabeculation, and in two patients the fistulas communicated with anomalous bronchi. One patient had anomalous bronchi and subsequently underwent lobectomy which showed microscopic findings of intralobar sequestration. The oesophagus showed localized tenting with its apex to the fistula and mild ipsilateral displacement in four patients.

Adult

Primary malignant tumor of the small intestine.

The records of 101 patients with primary small intestinal malignant tumor at NTUH, collected from 1960 to 1989, were reviewed. These patients represented 1.2% of the patients with gastrointestinal cancer at NTUH over the same period. Fourty-two (41.6%) of the cancer patients had lymphomas, 30(29.7%) had adenocarcinomas, 26 (25.7%) had leiomyosarcomas, and 3(3.0%) had carcinoid tumors. The average age at cancer presentation was 47.5 years (range from 3 to 96). The lymphoma patients had an average age of 35.1 years, while adenocarcinoma patients averaged 60.4 years of age. Leiomyosarcoma and carcinoid tumors averaged 51.2 years and 59 years, respectively. There were 65 male patients and 36 female patients, and there was a male predominance in all groups except for the leiomyosarcoma group which had an equal sex ratio. Generally speaking, the incidence rate for the areas involved were similar in the duodenum, jejunum and ileum. However, adenocarcinomas were more common in the duodenum (53%) and 45% of lymphomas were found in the ileum, as were the carcinoid tumors (66%). The most common presenting symptom was abdominal pain (62%), with bleeding second (32%). Obstruction and palpable mass together were present in 29% of the cases. Body weight loss was found in 25% of patients, and 14% of the patients presented with acute abdomen due to intestinal perforation. Laparotomy was the most common diagnostic procedure (60%). Preoperative diagnoses were possible in cases of duodenal and upper intestinal malignancies, but were rarely possible in patients with lower intestinal malignancies. Sixty-eight patients (68%) underwent tumor resection for palliation or cure. The operation mortality was 4%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

CT manifestations of peritoneal leiomyosarcomatosis.

Peritoneal leiomyosarcomatosis causes multiple discrete tumor nodules in the peritoneum, mesentery, and omentum with or without evidence of a primary site. The CT and pathologic findings in seven patients with this disease were reviewed. All seven patients had CT evidence of multiple, discrete peritoneal masses, and five patients showed a central low-attenuation area. CT grade of malignancy in peritoneal tumors was categorized as low (four patients) and high (three patients) on the basis of the degree of central necrosis of the tumors. The CT results correlated with the histopathologic grade of malignancy, although all tumors were grade 2 or higher histopathologically. Ascites and lymphadenopathy were not present in any of the patients. Liver metastases were identified in five patients with central necrosis of the metastases evident in four. The presence of liver metastases and the degree of central necrosis in the liver metastases did not correlate with the size or histologic grade of the primary tumor. Although uncommon, peritoneal leiomyosarcomatosis should be considered when CT shows multiple, discrete peritoneal masses with central necrosis and liver metastases in the absence of ascites and lymphadenopathy.

Adult

Advances in percutaneous nephrostomy.

Management of urologic patients is being gradually but dramatically altered with new advances in technical innovation and refinements of interventional uroradiology. The broadening of indications for percutaneous nephrostomy became possible only after it was learned that it is a safe and effective means of establishing access to the renal collecting system. Percutaneous stone extraction (Nephrolithotomy) and Endopyelotomy are now well established procedures. These techniques have clear advantages over the surgical treatment for the same conditions and will increase the quality of patient care and reduce health care cost.

Contraindications

Factors influencing the binding of calpain I to human erythrocyte inside-out vesicles.

The mechanism for binding of human erythrocyte calpain I to human erythrocyte inside-out vesicles was studied by immunoelectrophoretic blot analysis. Binding of calpain I to inside-out vesicles was observed both in the absence and presence of Ca2+. Moreover, in the absence of Ca2+, acidic proteins like casein, ovalbumin and calpastatin suppressed while basic proteins like arginase and lysozyme did not affect the binding of calpain I to inside-out vesicles. Here, we propose a model for the binding of calpain to the membrane.

Arginase

Percutaneous nephrostomy in the management of renal candidiasis.

A case of Candida infection of the kidney was successfully managed by percutaneous means. This case demonstrates that percutaneous nephrostomy is a simple, effective technique not only for drainage, extraction of fungus balls, and irrigation with amphotericin B, but also for examining the renal collecting system and obtaining urine samples for diagnostic culture verification. Because of the toxicity of antifungal drugs, the incorporation of this percutaneous technique into standard management will benefit the patient with a life-threatening renal fungal infection.

Candidiasis

Responses of vasopressin release in patients with cardiopulmonary bypass anesthetized with enflurane and morphine.

Changes in plasma level of arginine vasopressin (AVP), arterial pressure, and urine flow were studied before, during and after cardiopulmonary bypass (CPB) in 11 patients with congenital heart disease. Anesthesia was induced with thiopental sodium (3-5 mg/kg) and was maintained with enflurane (1.0-1.5%), 50% N2O in O2 and morphine (0.5 mg/kg). Concentration of plasma AVP increased slightly from 3.8 +/- 1.5 pg/ml after induction and increased 3-fold after sternotomy. Plasma AVP level increased to 132 +/- 26 pg/ml and 218 +/- 54 pg/ml after 5 and 60 min on CPB, respectively. When the circulation returned to normal, plasma AVP level decreased gradually but was still significantly higher at 24 hr (13.4 +/- 2.5 pg/ml). Marked osmolar diuresis was induced with mannitol in the priming solution used during the CPB: increases in urine flow, Na excretion and osmolar clearance. Possible mechanisms of marked increase in AVP release and differences of AVP responses during CPB reported by other investigators are discussed.

Adolescent

A case of acute superior mesenteric embolism successfully treated by embolectomy.

Superior mesenteric artery embolism is undoubtedly fatal unless operative intervention is promptly performed. The first case successfully managed by embolectomy in Taiwan is reported in this communication. The key to successful management lies in the early suspicion in patients with atrial fibrillation or recent myocardial infarction, presenting with sudden abdominal pain and an unremarkable physical examination. Abdominal angiography is strongly recommended; however, immediate laparatomy should not be postponed if angiography is not available. Early embolectomy is the only useful means of treatment to restore mesenteric circulation, preserve the bowel and rescue the patient. A 56-year-old woman was admitted with a 5-year history of rheumatic heart disease and atrial fibrillation. She had a sudden attack of severe abdominal pain 8 hours after cardiac catheterization. Abdominal examination was not remarkable and plain abdominal X-ray was negative, while bloody stools and leukocytosis developed 7 hours later. Superior mesenteric embolism was highly suspected and emergency laparotomy was performed. Successful embolectomy was carried out through the distal approach and the patient recovered completely without requiring small bowel resection. All branches of the superior mesenteric artery were demonstrated patent upon postoperative angiography.

Embolism

Diagnosis and management of complications of percutaneous nephrolithotomy.

The therapeutic management of the complications of percutaneous nephrolithotomy (PNL) depends on the early recognition of these complications. A review of 720 cases revealed the incidence of significant complications to be less than 4%. An algorithm was developed as a guideline for the diagnosis and management of complications of PNL. Early complications included transient bleeding (83 cases), extravasation of urine (52 cases), significant infection (11 cases [2 with septicemia and shock]), and migration of stone fragments into the retroperitoneum (7 cases). Nonrenal complications were present in less than 6% of these patients. These included pleural effusions or pneumothorax (24 cases) and lung atelectasis (19 cases). Late complications were seen in less than 2% of the patients. These included stricture of the ureter with obstruction (5 cases), A-V fistula with or without pseudoaneurysm (7 cases), and subcapsular hematoma (1 case). Therapeutic management included improvement of technique to the use of antibiotics to treat infection. The use of proper drainage and the placement of stent or catheter in the treatment and prevention of further complications has become an integral part of the algorithm for the treatment of complications of PNL. This algorithm recommends the proper diagnostic modality for the detection and evaluation of the extent of the complication. Once detected, the complications of PNL can be minimized with limited permanent changes.

Adolescent

Treatment of ureteropelvic strictures with percutaneous pyelotomy: experience in 62 patients.

Percutaneous pyelotomy (endopyelotomy) is an endoscopic technique for the management of ureteropelvic junction obstruction. In a series of 62 consecutive patients, the success rate (measured by symptom-free status and improved uroradiographic findings) was 85%, including both primary and secondary obstructions. All failures were apparent within 3 months of the procedure and required open surgery. There were two major complications during the procedure. Our experience indicates that percutaneous pyelotomy is an effective alternative to traditional open pyeloplasty and has a similar success rate, lower morbidity, and a shorter recovery time.

Adolescent