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Biomedical subjects

K C Wang

Publications and source records attributed to K C Wang.

At least 19 recordsLinked to original sources

Pathological changes in the liver of a senescence accelerated mouse strain (SAMP8): a mouse model for the study of liver diseases.

Liver disease is characterized by fatty liver, hepatitis, fibrosis and cirrhosis and is a major cause of illness and death worldwide. The prevalence of liver diseases highlights the need for animal models for research on the mechanism of disease pathogenesis and efficient and cost-effective treatments. Here we show that a senescence-accelerated mouse strain (SAMP8 mice), displays severe liver pathology, which is not seen in senescence-resistant mice (SAMR1). The livers of SAMP8 mice show fatty degeneration, hepatocyte death, fibrosis, cirrhotic changes, inflammatory mononuclear cell infiltration and sporadic neoplastic changes. SAMP8 mice also show abnormal liver function tests: significantly increased levels of alanine amino-transferase (ALT) and aspartate aminotransferase (AST). Furthermore, titers of murine leukemia virus are higher in livers of SAMP8 than in those of SAMR1 mice. Our observations suggest that SAMP8 mouse strain is a valuable animal model for the study of liver diseases. The possible mechanisms of liver damage in SAMP8 mice are also discussed.

Alanine Transaminase↗

Walnut extract inhibits the fibrillization of amyloid beta-protein, and also defibrillizes its preformed fibrils.

Fibrillar amyloid beta-protein (Abeta) is the principal component of amyloid plaques in the brains of patients with Alzheimer's disease. We have studied the effect of walnut extract on Abeta fibrillization by Thioflavin T fluorescence spectroscopy and electron microscopy. The walnut extract not only inhibited Abeta fibril formation in a concentration and time- dependent manner but it was also able to defibrillize Abeta preformed fibrils. Over 90% inhibition of Abeta fibrillization was observed with 5 microl of methanolic extract of walnut (MEOW) both after 2 and 3 days of incubation. The maximum defibrillization (91.6%) was observed when preformed Abeta fibrils were incubated with 10 microl of MEOW for 2 days. These results suggest that walnuts may reduce the risk or delay the onset of Alzheimer's disease by maintaining Abeta in the soluble form. Further studies showed that anti-amyloidogenic compound in walnut is an organic compound of molecular weight less than 10 kDa, which is neither a lipid nor a protein. Chloroform extract of walnut had no effect on Abeta fibrillization while MEOW and its 10 kDa filtrate inhibited Abeta fibrillization equally. It is proposed that polyphenolic compounds (such as flavonoids) present in walnuts may be responsible for its anti-amyloidogenic activity.

Amyloid↗

Novel lead generation through hypothetical pharmacophore three-dimensional database searching: discovery of isoflavonoids as nonsteroidal inhibitors of rat 5 alpha-reductase.

A hypothetical pharmacophore of 5 alpha-reductase inhibitors was generated and served as a template in virtual screening. When the pharmacophore was used, eight isoflavone derivatives were characterized as novel potential nonsteroidal inhibitors of rat 5 alpha-reductase. This investigation has demonstrated a practical approach toward the development of lead compounds through a hypothetic pharmacophore via three-dimensional database searching.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Childhood meningioma: unusual location, atypical radiological findings, and favorable treatment outcome.

OBJECTS: To investigate the characteristics of childhood meningioma, especially, locations, radiological findings, pathological features (including proliferative potential) and outcome, 11 children with meningiomas were retrospectively analyzed. RESULTS: Unusual location, large size, frequent calcification, and cyst formation were characteristic radiological findings. Gross total resection was achieved in 8 patients, and there was recurrence in 2. Gamma knife radiosurgery was performed on residual and recurrent tumors. MIB-1 indices tended to be high in large tumors. Nine patients had a Karnofsky Performance Scale of more than 70 during the follow-up period of 10 months to 19.5 years. Surgical treatment rendered 4 of 5 epileptic patients seizure free. The childhood meningiomas examined had unusual locations, atypical radiological findings, and various proliferative potentials. CONCLUSIONS: Complete resection is the treatment of choice. Gamma knife radiosurgery can be a good alternative for residual tumors and small recurrent tumors. The outcome of childhood meningiomas is good after surgery.

Adolescent↗

Is the re-closure of surgically induced open neural tube defect the repetition of primary neurulation? An experimental study with chick embryos.

It is well known that surgically induced open neural tube defects (ONTDs) tend to re-close in early embryonic stages. To investigate whether the process of re-closure is a repetition of primary neurulation, the morphological changes of surgically induced ONTDs were chronologically examined in early chick embryos. Longitudinal incisions of 3-somite length were made in the neural tubes of chick embryos at Hamburger and Hamilton stage 18 or 19. About half of the embryos showed complete closure of the skin on surgical microscopic examination. The re-closed neural tubes showed no remarkable differences from the controls on histological examination. The process of re-closure involved a zipper-like (ventral to dorsal) closure in the transverse sections of neural tubes. The results indicate that the re-closure of surgically induced ONTDs does not repeat the process of natural primary neurulation.

Age Factors↗

Cerebellar alterations induced by chronic hypoxia: an immunohistochemical study using a chick embryonic model.

A model of fetal aerogenic hypoxia was developed in which fertilized chicken eggs were half-painted with melted wax and incubated under normal conditions. The cerebellum of the hypoxic chick embryos at a later stage of development (E18-20) was analyzed immunochemically. Hypoxic insult resulted in considerable neurocytological deficits of the Purkinje cells and altered glial fibrillary acid protein (GFAP) immunoreactivity in the fetal cerebellum. Purkinje cells in the hypoxic embryos were marked by small cell size, poorly developed dendrites, low cell density, deletion and ectopia. On the other hand, enhanced GFAP immunoreactivity was found in astrocytes and Bergmann glia of the hypoxic embryos. Our results indicate that chronic hypoxia in the chick fetus can cause severe disorders of neuronal development as well as glial activation. We suggest that our hypoxic model of chick embryos could be an accessible animal model for further elucidating fetal hypoxia.

Animals↗

Intramedullary immature teratoma in a young infant involving a long segment of the spinal cord.

Intramedullary teratoma is a rare lesion, located in the majority of cases in the lumbosacral area, and such lesions involving an extensive area of the spinal cord in young infants have seldom been reported. We present the case of a 3-month-old girl with an intramedullary spinal immature teratoma extending from C-5 to T-12, which was totally removed. The patient had suffered from paraplegia for 15 days, after which spinal MRI revealed a heterogeneously enhancing intramedullary lesion. Biopsy of the lesion demonstrated mature intestinal tissue. After total removal of the tumor, paraplegia and sphincter disturbances improved. Intramedullary teratoma should be included in the differential diagnosis of holocord tumors in young infants with rapidly progressing symptoms and if found should be radically excised. This case also emphasizes the importance of histological diagnosis and demonstrates the possibility of neurological recovery even in the case of paraplegia lasting for more than 1 month in a young infant.

Diagnosis, Differential↗

MR diagnosis of cerebellar infarction due to vertebral artery dissection in children.

Posterior circulation infarction is uncommon in children. We describe the clinical presentation and radiological findings in two children with cerebellar infarction resulting from dissection of the vertebral artery. We emphasize that vertebral artery injury should be considered in a child with acute symptoms and signs of ischaemia in the posterior circulation. MRI and MRA may be helpful in the diagnosis of cerebellar infarction and vertebral artery abnormality.

Cerebellar Diseases↗

Gangliocytoma of the spinal cord: a case report.

We present a case of intramedullary spinal gangliocytoma in a 7-year-old girl who presented with scoliosis and progressive weakness of both legs. The tumour involved the whole spinal cord and medulla oblongata and was composed of inner cystic and outer solid components. On MRI, the solid portion of the lesion showed strong enhancement at the thoracolumbar level and mild enhancement at the cervical and medullary levels. Histological examination of the surgical specimen showed neoplastic ganglion cells arranged irregularly in benign normocellular glial background, which made a diagnosis of gangliocytoma.

Female↗

Intractable epilepsy associated with brain tumors in children: surgical modality and outcome.

OBJECTS: The aim of this study was to evaluate the role of surgical modality in children with brain tumors and intractable epilepsy. METHODS: Twenty-three patients who were treated for brain tumors and intractable epilepsy between January 1985 and March 1998 were retrospectively reviewed. The most common tumors were dysembryoplastic neuroepithelial tumors (n=9), oligodendrogliomas (n=6), and gangliogliomas (n=5). Six patients exhibited cortical dysplasia. The mean duration of follow-up was 43.4 months (range 12 to 125 months). Seizure outcome was more favorable (Engel's classes I and II) in patients with a complete resection of tumor (14/14 vs 6/9 for incomplete resection; P<0.05). There was no significant difference in seizure outcome between lesionectomy (n=13) and epilepsy surgery (n=10). The likelihood of requiring postoperative antiepileptic drugs was not influenced by the extent of resection or type of surgery. CONCLUSIONS: On the basis of this study, we conclude that the complete resection of these tumors can be an appropriate initial treatment for children with brain tumors who experience intractable epilepsy.

Adolescent↗

Radical excision of pediatric craniopharyngioma: recurrence pattern and prognostic factors.

The purpose of our study was to investigate the pattern of recurrence and the prognostic factors for recurrence of pediatric craniopharyngiomas after radical excision. A series of 36 patients with craniopharyngiomas (21 boys and 15 girls; age range 1-15 years; mean 7.3 years) were reviewed. All patients had undergone radical excision without radiotherapy. The mean follow-up period was 52 months (range 1-149 months). Tumors recurred in 14 patients within 83 months (mean 31.4 months). The overall 5-year recurrence-free survival rate was 55%. Regular neuroimaging follow-up detected tumor recurrence while the lesions were still small before symptoms developed (P<0.05). At the first surgical procedure, the optic nerve/chiasm (n=23) was the most common adhesion site. The most frequent sites of recurrence were the optic nerve/chiasm (n=6) and the pituitary fossa (n=6). Tumor location was the single significant clinical predictor of recurrence. The 5-year recurrence-free survival rate was 39% for those who had an intrasellar tumor component and 81% for those who did not (P<0.05). The Ki-67 labeling indices (LIs) of primary tumors did not have prognostic value for recurrence. Recurrent tumors tended to have higher Ki-67 LIs than their primary counterparts. On the basis of this study, we concluded that craniopharyngiomas with intrasellar components should be followed cautiously and the necessity for regular follow-up should be emphasized, even when the tumor is "totally" resected.

Adolescent↗

Major complications of operative and diagnostic laparoscopy for gynecologic disease.

STUDY OBJECTIVE: To compare complication rates of diagnostic and operative laparoscopy. Design. Retrospective study (Canadian Task Force classification II-2). SETTING: One medical center and three teaching hospitals. PATIENTS: Six thousand four hundred fifty-one women with various indications for laparoscopic diagnosis and/or laparoscopic surgery from January 1994 through June 1999. INTERVENTION: Diagnostic and operative laparoscopies. MEASUREMENTS AND MAIN RESULTS: Forty-two major complications occurred that directly resulted in one death. One patient had stomach injury, 3 had major vessel injuries, 5 had ureter injuries, 10 had intestinal injuries, and 23 had bladder injuries. The overall complication rate for all laparoscopies was 0.65% (42/6451); however, it rose to 0.80% (39/4865) for operative laparoscopy compared with 0.19% for diagnostic laparoscopy (3/1586; p <0.001, Fisher's exact test). CONCLUSION: Laparoscopic surgery is appropriate for managing various gynecologic diseases and has an acceptable complication rate. However, operative laparoscopy should be performed carefully because its rate of complications is significantly higher than that of diagnostic laparoscopy, especially for laparoscopic-assisted vaginal hysterectomy. (J Am Assoc Gynecol Laparosc 8(1):68-73, 2001)

Catheterization↗

Biological behavior and tumorigenesis of subependymal giant cell astrocytomas.

In spite of the benign nature of subependymal giant cell astrocytomas (SEGAs), some show massive hemorrhage, rapid growth, and tumor recurrence. This led us to investigate the biological behavior, cell dynamics, and tumorigenesis of SEGAs. All patients (4 men and 3 women; age range, 6-27 years; mean, 13.6 years) had features of tuberous sclerosis complex and obstructive hydrocephalus. One patient had intratumoral bleeding. In two patients, sequential neuroimaging showed a subependymal nodule growing to become a SEGA. All underwent surgical resection without radiation therapy. One tumor recurred and was treated surgically. There were no postoperative deaths. The presence of cytologic atypia, mitoses and vascular proliferation had no implication in terms of the clinical course. MIB-1 labeling indices were low (mean, 0.9), indicating low proliferative potential. Unexpectedly, bcl-2 staining was sparse and bax staining predominated in majority of cases. However, the mean value of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling index was low. Immunohistochemically, tumors were positive for both glial and neuronal markers. In the majority of our cases, the expression of p53 was low. Only one tumor was focally positive for tuberin. SEGAs have low proliferative potential and apoptotic activity, and exhibit features of mixed glial-neuronal differentiation. In contrast to p53, tuberin is suggested to be the tumor suppressor in this tumor.

Adult↗

Hemifacial seizure of cerebellar ganglioglioma origin: seizure control by tumor resection.

The cerebellum is known to have an inhibitory effect on seizures. Nevertheless, cerebellar dysplastic lesions can be epileptogenic. A 4-month-old infant had paroxysmal facial contractions; tachypnea and nystagmoid eyeball and tremulous movements were occasionally combined. These evolved to stereotypic clinical patterns and frequencies, which increased despite administration of antiepileptic drugs (AEDs). Magnetic resonance imaging (MRI) demonstrated a mass arising from the superior cerebellar peduncle, although video-scalp EEG monitoring revealed no abnormal findings. Positron emission tomography with [(18)F]fluorodeoxyglucose revealed focal hypermetabolism in the same area identified by MRI. A depth electrode implanted in the mass revealed focal spike-and-wave discharges. The lesion was partly removed; pathologic diagnosis was ganglioglioma. Because of incomplete seizure control and residual tumor visible on MRI, a second operation was performed. After complete excision of the tumor, the patient became seizure free without AEDs. This case confirms the presence of seizure originating from the cerebellum and emphasizes the need for the complete removal of an epileptogenic lesion.

Cerebellar Neoplasms↗

Reconstruction of posttraumatic long bone defect with free vascularized bone graft: good outcome in 48 patients with 6 years' follow-up.

We analyzed our clinical results in 48 patients (40 men) treated during 1990-1993 with free vascularized bone-graft reconstruction for bone defects, the follow-up being an average 6 (5-8) years. The bone defects were located in the femur (10), tibia (32), humerus (2), and forearm (4). We performed 41 fibula transfers, 4 iliac transfers, and 3 rib transfers in these patients. 3 patients required early revision surgery due to venous thrombosis. The average time needed for radiographic bone union was 4.2 months. Bone transfers to the lower extremity showed significantly more hypertrophy than those in the upper extremity. The functional outcome was good in 43 patients.

Adolescent↗

Antileukemic activity of Bidens pilosa L. var. minor (Blume) Sherff and Houttuynia cordata Thunb.

To evaluate the anti-leukemic activity of Bidens pilosa L. var. minor (Blume) Sherff and Houttuynia cordata Thunb., cytotoxicity tests with an XTT-based colorimetric assay were used. Five leukemic cell lines, namely L1210, U937, K562, Raji and P3HR1, were cultured with hot water extracts of B. pilosa var. minor or H. cordata. Hot water extracts of B. pilosa var. minor inhibited these five leukemic cells with IC50s between 145 microg/ml and 586 microg/ml. The effect was greatest on four cell lines, namely L1210, P3MR1, Raji and K562, with IC50s below 200 microg/ml and a selective index of more than 5. Hot water extract of H. cordata inhibited these five leukemic cells with IC50s between 478 microg/ml and 662 microg/ml. The selective index was between 1.5 and 2.1. B. pilosa var. minor was more effective than H. cordata in inhibiting most of the leukemic cells in our study. We suggest that B. pilosa L. var. minor (Blume) Sherff may prove to be a useful medicinal plant for treating leukemia.

Antineoplastic Agents, Phytogenic↗

Pathogenesis of lumbosacral lipoma: a test of the "premature dysjunction" theory.

Premature separation of the neuroectoderm from the ipsilateral surface ectoderm allowing mesenchymal tissue to invade into the central canal, or "premature dysjunction" theory, was proposed for the pathogenesis of dorsal type lumbosacral lipoma. To test this theory, the unilateral neural fold was incised using Hamburger and Hamilton stage 12 or 13 chick embryos. Among 35 embryos evaluated, 15 showed abnormal findings, and of these one showed findings which suggested lumbosacral lipoma: a back lump, blending of the neuroepithelium and mesenchyme through indistinct basement membrane and vertebral body abnormalities. The other 14 embryos showed abnormalities including blunt tails, open neural tube defects, incomplete closure of the dorsal neuroepithelium with intact skin, skin dimples, disorganized gray matter, scoliosis, ectopic neuroepithelium and an accessory spinal cord. The results revealed that the incision of the unilateral neural fold in the early chick embryo may produce a lesion suggestive of lumbosacral lipoma, a finding which supports the premature dysjunction theory. This method needs further refinement to overcome technical difficulties, high mortality, and a low yield before being adopted as an experimental model for lumbosacral lipoma.

Animals↗

Cytochemical study of the involvement of cell organelles in formation and accumulation of fibrillar amyloid in the pancreas of NORbeta transgenic mice.

Phosphatase ultrastructural cytochemistry was used to evaluate the participation of cytoplasmic organelles in the accumulation of fibrillar amyloid beta (Abeta) in exocrine acinar cells and in macrophages of the pancreas of transgenic mice overexpressing a carboxy-terminal fragment of Abeta protein precursor (ABPP). Nucleoside diphosphatase (NDPase) and glucose-6-phosphatase (G6Pase) were used as cytochemical markers of the endoplasmic reticulum (ER), thiamine pyrophosphatase (TPPase) as a marker of the Golgi apparatus (GA), and acid phosphatase (AcPase) as a marker of lysosomes. Monoclonal antibody 4G8 raised against the 17-24 aa sequence of human Abeta protein was used for immunogold localization of fibrillar Abeta. The results of this study indicate that the formation of Abeta in acinar cells occurs directly in the vacuolar areas of the rough ER (RER) without evident participation of the elements of the GA, whereas an intimate structural relation with primary lysosomes suggests their role in modification or digestion of the deposited amyloid. In macrophages, fibrillar amyloid was present in numerous cytoplasmic vacuoles located frequently in close proximity to flattened saccules of the ER. This structural pattern revealed similarity to that observed previously in microglial cells producing fibrillar PrP amyloid in scrapie-infected mice and Abeta in brains of human elderly patients and in Alzheimer's type brain pathology.

Acid Anhydride Hydrolases↗