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Biomedical subjects

C F Huang

Publications and source records attributed to C F Huang.

At least 55 records · Page 3Linked to original sources

Stereotactic radiosurgery for trigeminal schwannomas.

OBJECTIVE: Schwannomas that arise from the trigeminal nerve are rare and are usually managed by surgical resection. The role of radiosurgery in the care of patients with these basal tumors remains to be defined. METHODS: We reviewed the clinical presentation, management, and outcomes for 16 trigeminal schwannoma patients who underwent gamma knife stereotactic radiosurgery. Fifteen of the 16 patients presented with trigeminal sensory dysfunction. Nine patients had tumors in the region of the ganglion, six in the region of the trigeminal nerve root, and one in the region of the mandibular branch. Six patients had undergone one or more previous resections before radiosurgery. Ten underwent radiosurgery as the first procedure. The mean tumor volume was 5.3 cc (range, 1-17.8 cc). The mean tumor margin dose was 15.3 Gy (range, 12-20 Gy). RESULTS: During the average imaging follow-up of 44 months (range, 8-116 mo), the tumor control rate was 100% (regression in nine patients and no further tumor growth in seven patients). Five patients had improvement of clinical symptoms, and 11 remained unchanged. No new cranial nerve deficit developed in any patient. CONCLUSION: As a minimally invasive alternative to microsurgery, gamma knife radiosurgery proved to be an alternative primary or adjuvant strategy that controlled tumor growth, did not cause new deficits, and often improved presenting symptoms.

Adult↗

Stereotactic radiosurgery for brainstem metastases.

OBJECT: Brainstem metastases portend a dismal prognosis. Surgical resection is not part of routine management and radiation therapy has offered little clinical benefit. Radiosurgery provides a safe and effective treatment for many patients with brain metastasis, but its role in the brainstem has not been evaluated. In this study the authors examine the role of radiosurgery in the treatment of brainstem metastases. METHODS: The authors reviewed the outcomes after stereotactic radiosurgery in 26 patients with 27 brainstem metastases. Tumor locations included the pons (21 tumors) and midbrain (six tumors): 14 patients had additional tumors in other locations. Twenty patients presented with brainstem signs. The median dose to the tumor margin was 16 Gy (range 12-20 Gy). Twenty-four patients received fractionated whole-brain radiation therapy (WBRT) and 12 underwent additional chemotherapy or immunotherapy. The median follow-up time in these patients was 9.5 months (range 1-43 months). After radiosurgery, the local control rate in brainstem tumors was 95%. In one patient in whom the tumor initially decreased in size, tumor enlargement was seen 7 months later. The median survival time was 11 months after diagnosis and 9 months after radiosurgery. Thirteen patients improved, 10 were stable, and three deteriorated. Eventually, 22 patients died, 18 of progression of their extracranial disease, three of new tumor growth (including one hemorrhage into a new brain metastasis), and one of extracranial disease plus new brain tumor growth. CONCLUSIONS: Although they have slightly lower than the expected survival rates of patients with nonbrainstem tumors, patients with brainstem metastases may achieve effective palliation after stereotactic radiosurgery and WBRT.

Adult↗

Molecular cloning of Ras cDNA from Penaeus japonicus (Crustacea, decapoda): geranylgeranylation and guanine nucleotide binding.

A cDNA was isolated from the shrimp Penaeus japonicus by homology cloning. The shrimp hepatopancreas cDNA encodes a 187-residue polypeptide whose predicted amino acid sequence shares 85% homology with mammalian K-Ras 4B protein and demonstrates identity in the guanine nucleotide binding domains. Expression of the shrimp cDNA in Escherichia coli yielded a 21-kDa polypeptide with a positive reactivity towards the monoclonal antibodies against mammalian Ras. The GTP binding of the shrimp ras-encoded fusion protein was approximated to be 30000units/mg of protein, whereas the binding for GDP was 5000units/mg of protein. Fluorography analysis demonstrated that the prenylation of both shrimp Ras GDP and shrimp Ras GTP by protein geranylgeranyltransferase I of shrimp Penaeus japonicus exceeded the shrimp Ras nucleotide-free form by 10-fold, and fourfold, respectively; that is, the shrimp protein geranylgeranyltransferase I prefers to react with the shrimp ras-encoded p25 fusion protein in the GDP-bound form.

Alkyl and Aryl Transferases↗

Identification and purification of diphosphoinositol pentakisphosphate kinase, which synthesizes the inositol pyrophosphate bis(diphospho)inositol tetrakisphosphate.

Diphosphoinositol pentakisphosphate (PP-IP5) and bis(diphospho)inositol tetrakisphosphate (bis-PP-IP4) were recently identified as inositol phosphates which possess pyrophosphate bonds. The molecular mechanisms that regulate the cellular levels of these compounds are not yet characterized. To pursue this question, we have previously purified an inositol hexakisphosphate (IP6) kinase from rat brain supernatants [Voglmaier, S. M., et al. (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 4305-4310]. We now report the identification and purification of another novel kinase, diphosphoinositol pentakisphosphate (PP-IP5) kinase, which uses PP-IP5 as a substrate to form bis(diphospho)inositol tetrakisphosphate (bis-PP-IP4) in soluble fractions of rat forebrain. The purified protein, a monomer of 56 kDa, displays high affinity (Km = 0.7 microM) and selectivity for PP-IP5 as a substrate. The purified enzyme also can transfer a phosphate from bis-PP-IP4 to ADP to form ATP. This ATP synthase activity is an indication of the high phosphoryl group transfer potential of bis-PP-IP4 and may represent a physiological role for PP-IP5 and bis-PP-IP4.

Animals↗

Long term follow-up and late complications of 2-chlorodeoxyadenosine in previously treated, advanced, indolent non-Hodgkin's lymphoma.

BACKGROUND: The aim of this study was to determine the long term outcome and toxicities after the administration of 2-chlorodeoxyadenosine (2-CdA) to patients with previously treated, advanced, indolent non-Hodgkin's lymphoma (NHL). METHODS: Twenty-two patients (median age, 55 years) with relapsed or refractory low grade NHL (median disease duration, 2.8 years) were treated with 2-CdA by continuous infusion at 0.1 mg/kg/day over 5 or 7 days every 28 days, for a maximum of 6 cycles. RESULTS: The overall response rate was 45%. Two patients (9%) achieved a complete response (CR), 8 patients (36%) achieved a partial response, and 12 patients (55%) had no response. The two patients achieving CR have remained in CR for 46 and 38 months, respectively. Freedom from treatment failure at 24 months was 32%. Overall survival at 24 months was 59%. Three patients developed second malignancies: acute myelogenous leukemia (AML), myelodysplastic syndrome, and a cutaneous lymphoproliferative disorder. Fourteen patients have died after a median follow-up of 28 months (range, 3.9-49.2 months) due to progressive NHL (11 patients), infection (2 patients), and AML (1 patient). CONCLUSIONS: 2-CdA is an active agent for patients with previously treated, advanced, indolent NHL and may result in lasting remissions. Late complications following treatment may include delayed bacterial, fungal, or viral infection. Determination of whether the second malignancies that occurred in three patients reported herein were related to treatment with 2-CdA will require further study.

Adolescent↗

Preparation and cytotoxic effect of ceanothic acid derivatives.

Six ceanothane and 1-norceanothane derivatives (1, 2, 8-11) were prepared from ceanothic acid dibenzyl ester. These ring-A homologues of betulinic acid exhibited cytotoxic effects. Among these, 1-decarboxy-3-oxo-ceanothic acid (2) was found to be the most cytotoxic against OVCAR-3 and HeLa cancer cell lines, with an IC50 of 2.8 and 6.6 microg/mL, respectively, and an IC50 of 11.3 microg/mL against normal cell line FS-5.

Antineoplastic Agents, Phytogenic↗

Recurrent acute suppurative thyroiditis in a child: case report.

A 23-month-old girl presented with a history of persistent fever and growing left anterior neck mass following an upper respiratory tract infection. Laboratory studies revealed leukocytosis, elevated levels of the erythrocyte sedimentation rate and C-reactive protein, and a mild impairment of thyroid function. Thyroid scan showed a decreased radioactive iodine uptake of the left thyroid gland. Culture of the thyroid aspirate grew the mixed flora, viridans streptococci, Prevotella spp, and Peptostreptococcus magnus. She was discharged after a surgical drainage and a 14-day course of penicillin-G therapy. Unfortunately, she was readmitted for the resembling problems, the fever and progressing left anterior neck mass 3 months later. Culture of thyroid aspirate also grew the viridans streptococci. She recovered after a 14-day course of penicillin-G therapy. A left pyriform sinus fistula was found by barium esophagogram. A selective operation was performed 8 weeks later.

Acute Disease↗

[The analysis of biological characteristics for the tissue-plasminogen activator (t-PA) mutant engineered cell line].

The morphology of t-PA mutant engineered cell line FSGGI48 is similar to that of CHO-dhfr- cell in polygon. When aminopterin (MTX) concentration is 5 x 10(-6) mol/L, a part of cells become slim, but they are still in polygon. Therefore, the morphology of FSGGI48 cell line is normal. The expression level is 4000 IU/10(6) cells/24 h in serum-free medium. The cell line is bequeathed for three months in vitro and revived after freezing three months, the greater part of cells are stable. The expression level is 3000-4000 IU/10(6) cells/24 h. The assay of tumorigenesis shows that the cells, cellular DNA and purified products don't form tumors in nude mice. The cell line hasn't been contaminated by mycoplasma. The results of chromosomal analysis show that the chromosomal number of CHO-dhfr- cell is 20 and the abnormal rate is 6%. FSGGI48 cell line is same as CHO-dhfr- cell in chromosomal number and the abnormal rate is 15%-18%, it is normal in scope. Therefore, the engineered cell line FSGGI48 is excellent.

Animals↗

In vitro cytotoxic activity of 1-decarboxy-3-oxo-ceanothic acid in a human ovarian adenocarcinoma cell line.

The effect of a novel pentacyclic triterpene, 1-decarboxy-3-oxo-ceanothic acid (DOCA) on DNA synthesis, DNA degradation and programmed cell death was examined in human ovarian adenocarcinoma (OVCAR-3) cells. OVCAR-3 cells exposed to various concentrations of DOCA for 30 h displayed a dose-dependent inhibition of DNA synthesis. Morphologically, treatment with 10 microg/ml of DOCA for 24 h and 72 h resulted respectively in reduction in cell volume and condensation of nuclear structures. By agarose gel analysis, DNA fragmentation with the characteristic pattern of inter-nucleosomal ladder was observed after cells were treated with 2.5 microg/ml of DOCA for 24 h. Both cell death and DNA fragmentation caused by this compound were partially inhibited by the protein synthesis inhibitor cycloheximide, suggesting that the apoptotic process caused by DOCA requires synthesis of new proteins. On the other hand, no apparent double-stranded DNA breaks were detected after cells were incubated with 2.5 microg/ml of DOCA for 24 h, indicating that DNA damage was not a preceding event for apoptosis induced by this compound. Taken together, our results demonstrate that the cytotoxic effect of DOCA is mediated, at least in part, by the induction of apoptosis.

Adenocarcinoma↗

The usefulness of touch preparation cytological evaluation and prostatic capsule involvement in prediction of prostate cancer recurrence.

PURPOSE: Touch preparation cytology has been used in oncology as a technique to assist in predicting local tumor recurrence. We prospectively investigated the relationship between this cytological evaluation and the standard histological method of assessing specimens, measuring the distance from the tumor to the various anatomical boundaries and disease recurrence in radical retropubic prostatectomy patients. MATERIALS AND METHODS: In a prospective study of 91 consecutive clinical stages T1c and T2 cancer cases radical retropubic prostatectomy touch preparation cytology was performed intraoperatively in an anatomical fashion (apex, posterior, lateral right and left, and base). A single blinded cytopathologist reviewed all prostate touch preparation specimens and categorized them as malignant, benign or atypical cells. Benign or atypical cells were classified as negative cytology. Detailed histological margin analysis of the surgical specimens was also done in which distances between the tumor front, and prostate capsule (inner and outer edge) and surgical margins (apex, posterior, right and left lateral, and base) were measured. All specimens were re-staged by the same pathologist. Median followup was 38 months. Disease recurrence was determined biochemically (prostate specific antigen), and with bone scans, prostatic fossa biopsies and digital rectal examinations. RESULTS: Of the 91 specimens 25 were excluded from study because distance measurements could not be made for technical reasons. Multivariate analysis was performed on the remaining 66 patients based on the variables of stage, age, cytology status, distance from tumor to the inner prostatic capsule, distance from tumor to the surgical margin and postoperative Gleason sum. The only variable with independent prognostic value was postoperative Gleason sum (p = 0.04). Cytology status was not statistically significant (p = 0.07) nor were distance data to the inner capsule (p >0.05) and surgical margin (p >0.05). CONCLUSIONS: Although touch preparation cytology does not enhance prognostic information already provided by Gleason sum, it does correlate highly with postoperative Gleason sum. Other gross macroscopic variables, that is pathological stage, margin status and distance measurements, although lacking in independent predictive value, correlated with postoperative Gleason sum. The constancy of Gleason sum leads us to believe that the key to predicting prostatic cancer behavior lies not on the macroscopic but on the molecular or cellular level. Of the various factors analyzed in this study postoperative Gleason sum remains the most powerful predictor of recurrence risk.

Aged↗

Characterization of an ADP-ribosylation factor-like 1 protein in Saccharomyces cerevisiae.

ADP-ribosylation factors (ARFs) are highly conserved approximately 20-kDa guanine nucleotide-binding proteins that enhance the ADP-ribosyltransferase activity of cholera toxin and are believed to participate in vesicular transport in both exocytic and endocytic pathways. Several ARF-like proteins (ARLs) have been cloned from Drosophila, rat, and human; however, the biological functions of ARLs are unknown. We have identified a yeast gene (ARL1) encoding a protein that is structurally related (>60% identical) to human, rat, and Drosophila ARL1. Biochemical analyses of purified recombinant yeast ARL1 (yARL1) protein revealed properties similar to those ARF and ARL1 proteins, including the ability to bind and hydrolyze GTP. Like other ARLs, recombinant yARL1 protein did not stimulate cholera toxin-catalyzed auto-ADP-ribosylation. yARL1 was not recognized by antibodies against mammalian ARLs or yeast ARFs. Anti-yARL1 antibodies did not cross-react with yeast ARFs, but did react with human ARLs. On subcellular fractionation, yARL1, similar to yARF1, was localized to the soluble fraction. The amino terminus of yARL1, like that of ARF, was myristoylated. Unlike Drosophila Arl1, yeast ARL1 was not essential for cell viability. Like rat ARL1, yARL1 might be associated in part with the Golgi complex. However, yARL1 was not required for endoplasmic reticulum-to-Golgi protein transport, and it may offer an opportunity to define an ARL function in another kind of vesicular trafficking, such as the regulated secretory pathway.

ADP-Ribosylation Factors↗

Early histopathology of small intestinal discordant xenografts.

A descriptive study of a new model enabling serial biopsies of ongoing hyperacute rejection of small intestinal discordant xenografts is presented. In a series of guinea-pig-to-Lewis rat small bowel xenotransplants (n=7), aboral free ends of Thierry-Vella loops constructed from the graft were sequentially biopsied at one-minute intervals up to ten minutes post-reperfusion and less frequently thereafter. In a guinea pig-to-guinea pig (n=6) isograft series, biopsy controls for preservation/ischemia-reperfusion injury were obtained. Xenoantibody sequestration in this model was evaluated in a separate series of transplants, utilizing an ELISA assay for rat anti-guinea pig natural antibodies. Pathologic evaluation revealed a unique series of events characterized with microcirculatory failure and thrombosis progressing from the submucosal vasculature to the lumen. Within the system's detection limits, complement deposition and P-selectin expression occurred as early as one minute post-reperfusion, preceding the staining for IgM and IgG. Using rat serum ELISAs, no significant difference in xenoantibody sequestration was detected between the xenograft and isograft groups. The guinea pig-to-rat discordant small bowel xenotransplantation is an efficient small animal model to dissect the very early pathophysiologic events during hyperacute rejection.

Animals↗

Gestational trophoblastic disease metastatic to the brain.

PURPOSE: To evaluate clinical characteristics, treatment technique, and results in patients with gestational trophoblastic disease metastatic to the brain. MATERIALS AND METHODS: From 1962 to 1994, 26 (4.1%) of 631 patients who underwent treatment for trophoblastic disease had or developed evidence of brain metastases (patients were aged 14-43 years). All patients received multiagent systemic chemotherapy and whole-brain irradiation. Total doses of radiation were 2,386-4,000 cGy (200-300 cGy per fraction). No patient received intrathecal chemotherapy. Patients were divided into three groups: group A, symptomatic brain metastases at presentation; group B, asymptomatic or minimally symptomatic brain disease at presentation; and group C, development of brain metastases during systemic chemotherapy. RESULTS: The overall 5-year actuarial survival rate was 51%. Multivariate analysis findings indicated that age, preceding pregnancy event, human chorionic gonadotropin level, World Health Organization score, performance of craniotomy, and number of brain metastases did not influence survival. The difference in the 5-year overall survival rates between groups A (39%) and B (100%) was significant (P = .03). CONCLUSION: Gestational trophoblastic disease metastatic to the brain is curable with systemic chemotherapy and whole-brain irradiation. The authors suggest treatment with steroids, chemotherapy (etoposide, high-dose methotrexate [1 g/m2], dactinomycin, cyclophosphamide, and vincristine sulfate), and concurrent whole-brain irradiation (3,000 cGy in 200-cGy fractions).

Adolescent↗

Purification of the delta isoenzyme of protein kinase C from the hepatopancreas of the shrimp Penaeus monodon with phosphorylation on tyrosine residues.

The delta isoenzyme of protein kinase C (PKC-delta), purified from the plasma membrane of the hepatopancreas of the shrimp Penaeus monodon is specifically phosphorylated at tyrosine residues, as demonstrated by specific dephosphorylation by phosphotyrosyl protein phosphatase from the hepatopancreas of the shrimp Penaeus monodon. The specific activity of purified PKC-delta was 200 units/mg of protein. The subunits of M(r) 66,000, 62,000, and 58,000 of PKC-delta were not autophosphorylated after the addition of phosphatidylserine and diolein. However, the purified PKC-delta was active and catalyzed the phosphorylation of myelin basic protein. The kinase activity of the purified PKC-delta could be decreased after treatment with phosphotyrosyl protein phosphatase.

Animals↗

The depolarization response element in acetylcholine receptor genes is a dual-function E box.

All acetylcholine receptor subunit genes contain E boxes and are blocked by membrane depolarization. We have used transfected C2C12 myogenic cells to investigate the response, to electrical stimulation and KCl, of wildtype and mutant regulatory regions of the chick acetylcholine receptor alpha, gamma and delta subunit, and the mouse MLC genes. Point mutations revealed that E boxes function as activating elements targeted by the depolarization signal. These experiments suggest, and insertion of a depolarization response element into an unrelated promoter confirms, that plasma membrane depolarization switches the depolarization response element from an activating to a repressive mode.

Action Potentials↗

The role of the CANNTG promoter element (E box) and the myocyte-enhancer-binding-factor-2 (MEF-2) site in the transcriptional regulation of the chick myogenin gene.

We have carried out an analysis of 833 bp of the chick myogenin gene 5' flanking sequence. A 131-bp segment of this upstream region, which contains a CANNTG promoter element (E box) and a myocyte-enhancer-binding-factor-2 (MEF-2) site, acts as a full promoter. It resembles the human and the mouse myogenin promoters in the structure and disposition of regulatory elements, including a TATA box and the transcription start site. Examination of eight myogenic factor/E protein combinations cotransfected with several myogenin promoter constructs into HeLa cells, reveals that the chick myogenin/E2-5 combination maximally activates the myogenin promoter. This activation is mediated through the E box motif; the MEF-2 site limits the factor combinations that can activate the myogenin promoter and enhances activation by myogenin/E2-5. We have found previously that activation of protein kinase C inactivates the transcription of the chick myogenin gene [Huang, C.-F., Neville, C. M. & Schmidt, J. (1993) Control of myogenic factor genes by the membrane depolarization/protein kinase C cascade in chick skeletal muscle, FEBS Lett. 319, 21-25]. In this study, we show that the activation of protein kinase C inhibits the factor bound to the E box, which thereupon negatively regulates the activity of the MEF-2 binding protein.

Animals↗

The zeta protein kinase C isoform from the testis of the grey mullet Mugil cephalus with a specific reaction protein of M(r) 48,000 on oolemma.

The zeta protein kinase C isoform (PKC-zeta) was purified from the testis of the grey mullet Mugil cephalus and has relative masses (M(r)) of 65,000 and 63,000. The subunits of PKC-zeta from spermatozoa degenerated to M(r) 58,000 and 53,000 after continuous freezing and thawing. Proteins of M(r) 48,000 on the oolemma of the grey mullet Mugil cephalus were found to be the reaction proteins of the PKC-zeta from spermatozoa.

Amino Acid Sequence↗

A somatic cell genetic method for identification of untargeted mutations in the glucocorticoid receptor that cause hormone binding deficiencies.

Mouse T lymphoma cell line W7MG1, which is killed by physiological concentrations of glucocorticoid agonists, was used as a convenient genetic system for isolating sublines containing mutant glucocorticoid receptors (GR) with hormone-binding deficiencies. Partially hormone-resistant cell clones were derived from chemically mutagenized cell populations by selecting for growth in moderate concentrations of dexamethasone (Dex) and then screening for failure to grow in high Dex concentrations. Such clones are likely to have mutant GR. In GR cDNA clones from the partially resistant cell sublines, three different functionally significant mutations in the hormone-binding domain were identified: Leu-569 changed to Phe (L569F), Leu-670 to Phe (L670F), and Met-672 to Ile (M672I). Dose-response analyses with Dex and affinity labeling studies with dexamethasone 21-mesylate in transiently transfected cells indicated that all three mutant GR species had hormone-binding deficiencies. However, at saturating Dex concentrations the mutant and wild type GR activated a hormone-inducible reporter gene to the same extent; thus, these three mutations did not affect the ability of GR to activate transcription of the reporter gene after hormone was bound. In dose-response curves conducted with several glucocorticoid agonists, mutations L670F and M672I caused no change in ligand-binding specificities, while mutation L569F caused a modest change in specificity. Quantitative hormone-binding studies conducted with mutant GR synthesized in cell-free reactions showed that mutant GR species L569F and M672I had reduced Dex-binding affinities both at 0 C and at 22 C in the presence of molybdate. In contrast, for the L670F mutant, which exhibited the severest deficiency in vivo, the hormone-binding deficiency in the cell-free system was evident only at 26-37 C and primarily in the absence of molybdate. We propose that the L670F GR is an activation-labile type of mutant, which binds hormone normally in the presence of heat shock protein 90 but loses hormone rapidly after dissociation from heat shock protein 90. These three mutations define two new subregions of the GR polypeptide that are important for hormone binding.

Amino Acid Sequence↗