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Biomedical subjects

W C Shen

Publications and source records attributed to W C Shen.

At least 19 recordsLinked to original sources
PubMed1992

Brefeldin A enhances receptor-mediated transcytosis of transferrin in filter-grown Madin-Darby canine kidney cells.

The effects of brefeldin A (BFA) on transferrin (Tf) transcellular transport, Tf receptor (TfR) distribution, and TfR-mediated endocytosis in filter-grown Madin-Darby canine kidney (MDCK) cells were studied. BFA (1.6 micrograms/ml) markedly enhanced the transcytosis of 125I-labeled Tf (125I-Tf) in both apical-to-basal and basal-to-apical directions; yet, BFA did not enhance the transcytosis of either native horseradish peroxidase (HRP) or membrane-bound HRP-poly(L-lysine) conjugates. Furthermore, this enhanced transcytosis of 125I-Tf was abolished either by competition with excess unlabeled Tf or by incubation at temperatures less than or equal to 25 degrees C. In addition, BFA treatment to MDCK cells: (a) increased 125I-Tf specific binding to the apical membrane and decreased 125I-Tf specific binding to the basal membrane; (b) decreased TfR recycling at the basolateral membrane; (c) altered the apical/basolateral distribution of TfRs in favor of the apical side; and (d) markedly increased 59Fe extraction, but not transcytosis, from apically endocytosed 59Fe-loaded Tf. These effects are consistent with a model in which BFA alters the traffic pattern of internalized Tf by decreasing basolateral TfR recycling, while diverting the nonrecycled fraction to the apical side of the cell. Our results indicate that, unlike the reported inhibition of polymeric IgA transcytosis (Hunziker, W., Whitney, J. A., and Mellman, I. (1991) Cell 67, 617-627), BFA can enhance the transcytosis of Tf in MDCK cells. Thus, by altering the intracellular traffic of ligand-receptor complexes, BFA can elicit either a decrease or an increase in transcytosis depending on the nature of the intracellular receptor processing.

Animals↗
PubMed1992

Polarity in the transcytotic processing of apical and basal membrane-bound peroxidase-polylysine conjugates in MDCK cells.

A conjugate of horseradish peroxidase (HRP) to poly(L-lysine) (PLL) was used to characterize a non-lysosomal proteolytic compartment in the MDCK Strain I epithelial cell line. This compartment is expressed in a polar fashion, and is capable of degradation of the PLL moiety in the conjugate followed by release of HRP via a basal-to-apical, but not apical-to-basal, transcytotic pathway. This uptake, cleavage, and transport process appears to require approximately 2 hr, as there is a 2 hr lag-time between conjugate administration to the basal surface and HRP release to the apical medium. Monensin (10 microM) failed to inhibit this process, indicating that participation of the trans-Golgi network (TGN) in the trafficking of internalized conjugate is not the rate-determining step. Inhibition of HRP transport was found to be elicited by 50 micrograms/ml leupeptin, but only when applied to the basal surface. Brief trypsinization of either the basal or apical surfaces of cells preloaded with HRP conjugate showed no appreciable inhibitory effect on the apical release of HRP, indicating that an intracellular compartment rather than surface-bound enzymes is responsible for the degradation of the PLL moiety in the conjugate. Our results demonstrate the presence of an intracellular proteolytic compartment which is accessible in the basal-to-apical, but not apical-to-basal, transport pathway; and this compartment can be exploited for the transcytosis of membrane-bound molecules.

Animals↗
PubMed1992

Locations of cerebral infarctions in tuberculous meningitis.

The locations of cerebral infarctions were studied in 14 patients with tuberculous meningitis (TBM) and 173 patients with noninflammatory ischemic stroke (IS). In patients with TBM, 75% of infarctions occurred in the "TB zone" supplied by medial striate and thalamoperforating arteries; only 11% occurred in the "IS zone" supplied by lateral striate, anterior choroidal and thalamogeniculate arteries. In patients with IS, 29% of infarctions occurred in the IS zone, 29% in the subcortical white matter, and 24% in (or involving) the cerebral cortex. Only 11% occurred in the TB zone. Bilaterally symmetrical infarctions of the TB zone were common with TBM (71%) but rare with IS (5%).

Adult↗
PubMed1992

Tissue localization of methotrexate-monoclonal-IgM immunoconjugates: anti-SSEA-1 and MOPC 104E in mouse teratocarcinomas and normal tissues.

Methotrexate (MTX) was coupled to the tumor-targeting monoclonal IgM, anti-SSEA-1 and the non-targeting myeloma IgM, MOPC 104E. At 24-h intervals following injection, drug deposition in MH-15 teratocarcinomas and in several normal tissues was followed by immunoperoxidase microscopy using the M16 monoclonal antibody to MTX. MTX-anti-SSEA-1 was deposited on the surface and in the interior of living tumor cells 24 h after injection; at 48 h and after, only low-level binding to necrotic tissue was found. There was no significant gradation in staining from the outside to the interior of the tumors. In tumors, the control MOPC 104E immunoconjugate was detectable only in necrotic tissue. Binding to SSEA-1-expressing normal tissues was undetectable, except for pericryptal fibroblasts in the small intestine. No significant pathology was found in normal tissues that are SSEA-1 positive. High levels of the immunoconjugate were detected in the liver, where MTX was found predominantly in Kupffer cells and possibly in hepatocytes; again, no significant morphological changes were associated with this retention. Thus tumor-associated antigens can be suitable targets for antibody-drug conjugates even when present in normal tissues and in large quantities, provided that the antigens in normal tissues are inaccessible. Moreover, deposition in viable tumor tissue can be assessed using monoclonal antibodies to methotrexate.

Animals↗
PubMed1992

MRI of sequela of transverse myelitis.

A 4-year-old boy developed acute paraplegia, associated with sensory impairement and bowel and urinary dysfunction after an URI. MRI showed diffuse hyperintensity in T2WI in the spinal cord below the T6 level. Acute transverse myelitis was diagnosed based on the clinical presentations and MRI findings. The patient had poor recovery and two months later, a follow-up MRI disclosed a severe diffuse atrophic change of the spinal cord in the affected segment.

Acute Disease↗
PubMed1992

Differential expression of Hz-1 baculovirus genes during productive and persistent viral infections.

Hz-1 viral RNA transcription was studied during productive and persistent infections. The RNAs were localized to 10- to 30-kb regions within the viral genome, and the timing of their expression was determined. During productive infections, we detected 101 virus-specific transcripts that could be grouped into three categories by time of appearance. At 2 h postinoculation (p.i.), a total of 34 virus-specific transcripts were detected. An additional 51 and 16 virus-specific transcripts appeared between 4 and 6 h p.i. and at 8 h p.i., respectively. After 8 h, no new transcripts were found. Under conditions of persistent infection, we detected only one viral persistency-associated transcript (PAT1). The region of the viral DNA which encodes PAT1 was cloned. During productive infections, three transcripts were derived from this region. Each had the same polarity as PAT1. One of them was of the same size as PAT1 and had similar, if not identical, 3' and 5' ends. This report provides detailed and very useful information concerning sequentially expressed transcripts of the Hz-1 baculovirus.

Animals↗
PubMed1992

[Intracranial germ cell tumors].

We report on 19 cases of intracranial germ cell tumors, including 12 male and 7 female patients; the average age was 16.5 +/- 4.9 years. These tumors included germinoma in 15 cases, yolk sac tumor in 3 cases, embryonal cell carcinoma in 1 case, and mixed tumor in 3 cases. Each of 5 cases had 2 to 3 different kinds of tumor cells, either in one tumor or in different tumors. The locations of tumors were pineal region in 13 cases, suprasellar region in 3 cases, basal ganglion-thalamus in 3 cases, and cerebral hemispheres in 4 cases. Six of them had 2 or more locations. One case had spinal seeding and extraneural metastasis to the liver, retroperitoneum and neck lymph nodes. Eighteen cases received CT scan and 6 cases received MRI examinations, all the tumors had good enhancement by iodium content contrast medium in CT and Gadolinium-DTPA in MRI. Alfa-fetoprotein was elevated in yolk sac tumor, AFT and HCG were elevated only slightly or remained normal in germinoma. Germinomas had good response to radiation therapy and chemotherapy, while nongerminoma had poor response and worse prognosis.

Adolescent↗
PubMed1992

[Detection of the myelination process of Chinese infants by 1.0T MRI].

To establish the myelination process of brain of Chinese infants, our study consisted of seventy-five infants ranging in age from 5 days to 2 years old. They were studied with a 1.0 T superconductive MRI. In the new born, myelination could be seen in the brainstem, middle cerebellar peduncle, and posterior limb of the internal capsule in both T1WI and T2WI. Then the myelination process rapidly progressed month by month. Myelination of the centrum semiovale and optic radiation could be seen in T1WI in the newborn up to 3 months old, and in T2WI at 3-5 months old. The myelination of the splenium and the genu of corpus callosum were seen at 3-6 months in T1WI and 5-6 months in T2WI. Myelination of the occipital lobe and frontal lobe were seen at 3-6 months and 5-10 months in T1WI, and 8-14 months, 10-16 months in T2WI respectively. In 7-10 months, the brain appeared as an "early adult pattern" in T1WI; while, in T2WI, the brain appeared as an "early adult pattern" at 14-18 months old. The understanding of the myelination process in infants is important and essential for the judgement of the infantile brain and for the diagnosis of many CNS diseases of infants.

Age Factors↗
PubMed1992

Dural arteriovenous malformation of the transverse sinus with sinus occlusion: report of a case.

We report a case of dural arteriovenous malformation (AVM) of the transverse sinus with sinus occlusion. This 49-year-old man developed right parietal lobe dysfunction with acute onset. Computed tomography and magnetic resonance imaging (MRI) showed a non-hemorrhagic venous infarct in the subcortical white matter of the right parietal lobe, and diffusely dilated subcortical veins. Thrombosis of the right internal jugular bulb was also revealed on MRI. Cerebral angiography showed a dural AVM in the posterior fossa with occlusion of the right transverse sinus and retrograde venous drainage into the superior sagittal sinus, causing diffuse engorgement of the superficial cortical and the deep intramedullary veins. The focal neurologic deficits in this case were due to a non-hemorrhagic venous infarct in the subcortical white matter of the right parietal lobe secondary to retrograde cortical venous drainage.

Dura Mater↗
PubMed1992

[CT and MRI of parasellar cavernous hemangioma in two cases].

Extracerebral cavernous hemangioma is a rare entity, only 51 cases have been reported up to 1991. Most of the extracerebral cavernous angiomas occur in the parasellar region and easily extend to the sella; with CT and MRI views entirely different from those of intracerebral cavernous hemangiomas. The CT scan shows a good, homogeneous enhanced tumor, similar to a meningioma, yet lacking calcification or bony hyperostosis. In MRI, the characteristic findings of extracerebral cavernous hemangioma are the very high signal intensity in the T2 weighted image, and strong homogeneous enhancement by Gadolinium-DTPA. Here we report two cases of parasellar cavernous hemangioma. A 68-year-old male patient shown to have a dumbbell tumor in the parasellar and sellar regions by CT scan, showed a high density before contrast, and good enhancement by an iodine contained contrast medium. The tumor had a very high signal intensity in the T2 weighted image of MRI and a good, homogeneous enhancement by Gadolinium-DTPA, yet a carotid angiogram showed it was avascular. Surgical removal was abandoned in view of the probability of massive bleeding. The second case was a 34-year-old man, who had had a skin hemangioma on the right side of the face since his childhood. For the past 3 months, he had suffered from ptosis, and limitation of eye movement which was found to be due to 3rd and 4th cranial nerve palsy. CT showed a good enhanced tumor mass in the left side of the parasellar region with sellar extension. MRI also showed a high intensity in T2WI and good, homogeneous enhancement by Gadolinium-DTPA. A carotid angiogram revealed some tumor stain. Surgical removal. in this case, was also impossible due to its intracavernous sinus location and the probability of massive bleeding.

Adult↗
PubMed1991

Isolation of variants of Chinese hamster ovary cells with abnormally low levels of GSH: decreased ability to cleave endocytosed disulfide bonds.

Mutants of Chinese hamster ovary cells were selected for resistance to a 3 hour exposure to 4 microgram/ml N-methyl-N'-nitro-N-nitrosoguanidine and tested for glutathione (GSH) levels. Six of eight clones that survived the initial treatment had reduced GSH levels ranging from 26 to 61% of wild-type values. These eight cell lines were tested for their susceptibility to a drug conjugate in which methotrexate (MTX) is disulfide-linked to poly(D-lysine) (MTX-SS-PDL) to test their capacity to cleave the endocytosed disulfide bond and release free MTX from this otherwise undegradable drug conjugate. We had shown that wild-type cells were killed by approximately 1 x 10(-7) M MTX given as free drug, as MTX-poly(L-lysine) or as MTX-SS-PDL, but were not affected by MTX-poly(D-lysine). All six lines with abnormally low levels of GSH were resistant to MTX-SS-PDL. The variants with the lowest levels of GSH (MNR-5 and MNR-10) were tested further and showed near-normal sensitivity to MTX and MTX poly(L-lysine). As expected, both lines were hypersensitive to melphalan. They were, however, normally sensitive to diphtheria toxin and ricin, indicating that some cleavage of the interchain disulfides in these protein toxins occurs even when cellular GSH is abnormally low. The lesser GSH requirement for toxin activation may be due to their extraordinary potency.

Animals↗
PubMed1991

Effects of deoxycholate on the transepithelial transport of sucrose and horseradish peroxidase in filter-grown Madin-Darby canine kidney (MDCK) cells.

Madin-Darby canine kidney (MDCK) epithelial cells grown on microporous polycarbonate filters were used as a model system to investigate the mechanisms of enhancement by deoxycholate in the transepithelial transport of horseradish peroxidase (HRP) and 14C-sucrose. Deoxycholate at 0.025% had no effect on the transepithelial electrical resistance (TEER); a fivefold enhancement on the transepithelial transport of HRP, but not on that of 14C-sucrose, was observed. Deoxycholate at 0.05% induced a reversible decrease of TEER; a 2- and 50-fold enhancement on the transepithelial transport of 14C-sucrose and HRP, respectively, was observed. At 0.1%, deoxycholate induced an irreversible decrease in TEER and the epithelial barrier in the cell monolayer was completely eliminated. A 3.3-fold increase in cellular uptake in HRP, but not in 14C-sucrose, was also observed in the presence of 0.025% deoxycholate. The increase in cellular uptake was abolished when HRP was conjugated to polylysine. These results suggest that deoxycholate can increase the transepithelial transport by at least two different mechanisms, i.e., a transcellular pathway, possibly due to the enhancement of cellular uptake of selective molecules, and a nonselective paracellular pathway, due to the loosening of tight junctions by deoxycholate at higher concentrations.

Animals↗
PubMed1991

Polylysine conjugates of Bowman-Birk protease inhibitor as targeted anti-carcinogenic agents.

Bowman-Birk protease inhibitor (BBI), an 8000 mol. wt polypeptide with anti-carcinogenic activity, was coupled to poly(D-lysine) (BBI-SS-PDL) and poly(L-glutamate) (BBI-SS-PLG) with a disulfide-cross-linking agent, N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP). In vitro transformation assays showed that BBI-SS-PDL, but not BBI-SS-PLG, retained the full anticarcinogenic activity of BBI. When administered i.v. to Balb/c mice, a selective localization in the lungs was found with BBI-SS-PDL but not with BBI or BBI-SS-PLG. At 30 min, 3 h and 24 h after the injection of BBI-SS-PDL, the amounts of BBI in the lungs were 118%, 74% and 19% of the injected dose/g of tissue respectively. At the same time points, the amount of radioactivity in the lungs of mice injected with BBI was 5%, 3% and 1% of the injected dose/g of tissue respectively. Therefore, higher amounts of BBI could be targeted to the lungs by injecting BBI as a PDL conjugate. BBI-SS-PDL was also retained in the lungs for a longer period of time than free BBI. In previous studies, BBI has been shown to suppress lung carcinogenesis. The results presented here suggest that BBI-SS-PDL could be more effective than BBI as an anti-carcinogenic agent for the lung.

Animals↗
PubMed1991

[Detection of physiological deposition of iron in the brain using 1.0-T high field MR].

It has been well documented that high field magnetic resonance imaging can detect the location of physiological deposition of iron in the brain; such as in the globus pallidus, red nucleus, substantia nigra and dentate nucleus. The areas depict very low signal intensity in the long TR and the long TE imaging (T2 weighted image), because the iron enhances the T2 relaxation time. The purpose of this study was to determine the detectability of iron deposition in the brain by our 1.0-T high field MR, compared with 1.5-T MR which was used by most authors. We collected 160 MRI cases of the brain, and observed also signal void areas in the basal ganglion, brainstem or cerebellum. Our T2WI was TR 2000-3000 msec, TE 80-120 msec. We found that the 1.0-T MR clearly detected the iron deposition in the globus pallidus, red nucleus, substantia nigra and dentate nucleus of adults, with additional areas in the putamen and caudate nucleus of aged people. Shortcomings of the 1.0-T MRI for detecting iron deposition include: the margin of iron deposition was not very sharp in some cases, and for children under detectability was markedly inferior to the 1.5-T MR.

Adolescent↗
PubMed1991

Internal carotid artery occlusion in painful ophthalmoplegia.

Two patients with left painful ophthalmoplegia, caused by infiltrating lesion in left superior orbital fissure and/or cavernous sinus, subsequently developed left cerebral infarction associated with occlusion of the proximal portion of left internal carotid artery demonstrated by CT and angiogram. It thus is worthy to remind that painful ophthalmoplegia may have the possibility of resulting in cerebral infarction associated with carotid occlusion.

Aged↗
PubMed1991

Magnetic resonance imaging in two patients with radiation myelopathy.

Findings of magnetic resonance imaging (MRI) in 2 patients with radiation myelopathy are reported. One patient developed Brown-Séquard syndrome 7 months after radiotherapy for carcinoma of the nasopharynx. MRI done 8 months after clinical manifestations revealed long segmental enlargement of the cervical cord, low signal intensity on T1-weighted images and high signal intensity on T2-weighted images of the cervical cord. The other patient presented with bulbar palsy and Brown-Séquard syndrome 4 years after radiotherapy for carcinoma of the nasopharynx. MRI done 1 month after clinical manifestations showed a high signal intensity area on T2-weighted images of the medulla oblongata and the higher cervical cord. These findings corresponded well with the neurological level. In a proper clinical setting, findings of MRI may be helpful in the diagnosis of radiation myelopathy.

Adult↗
PubMed1991

[MRI of white matter pathways].

CT scan shows some relatively large white matter pathways such as corpus callosum or internal capsule, while MRI provides more sophisticated display of cerebral white matter pathways, based partly on difference in the water content, which improves contrast resolution of structures that cannot be appreciated on CT scanning. The white matter shows slightly high signal intensity in T1WI as compared with the peripheral gray matter. In contrast, it is relatively low signal intensity in long TR sequence. The signal intensity is correlated with myelination, density of myelin fibers and possibly iron deposition. In this study, we collected data on 30 patient, aged from 3 to 60 years average 38 years of normal MRI study of the brain. We routinely obtained T1 Weighted image (T1WI, TR/TE 500-600/20 msec), dual echoes image of proton density image (PDI, TR/TE 2000-3000/20 msec), T2 weighted image (T2WI, TR/TE 2000-3000/80-120 msec), in axial and coronal sections. In some cases sagittal section was also imaged. We identified the white matter pathways based on the data from the axial and coronal sections of 2 autopsy specimens. We also consulted several textbooks and literature reviews of gross and MRI anatomy. The following white matter pathways could be clearly observed on MRI: 1. Projection fibers: corona radiata and internal capsule; 2. Commissural fibers: corpus callosum and anterior commissure; 3. Associated fibers: superior occipito-frontal fasciculus, superior longitudinal fasciculus, ucinate fasciculus, cingulum bundle, optic radiation fornix and mammillothalamic tract.

Adolescent↗