Folylpoly-gamma-glutamate synthetase.
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Biomedical subjects
Publications and source records attributed to J C Hsu.
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To demonstrate the importance of early detection and diagnosis of acute acalculous cholecystitis, 34 patients with this disease, were studied retrospectively. Twenty patients had a delay between the onset of symptoms and operative intervention, exceeding 48 hours; five of them were found to have a perforated gallbladder during operation; however, no such complication was encountered in the 14 patients who underwent surgical treatment within 48 hours of onset. Sixteen patients had post-operative complications, and four patients who died produced in a mortality rate 11% (4/34). Three mortality cases had coexisting cardiovascular disease and the operation was also delayed for more than 48 hours.
We report two cases of malignant lymphoma of the breast. Extensive investigation on both, demonstrated only a neoplastic lesion confined within the breast. One was managed by local excision, systemic chemotherapy and adjuvant radiotherapy; the other was managed by a modified radical mastectomy, adjuvant radiotherapy and therapeutic chemotherapy. Both of them achieved complete remission 3 years and 1.5 years respectively after management.
Monoclonal antibodies, D2 and 4G11, selected by the autoantiidiotypic approach following injection of thyrotropin (TSH) into mice, mimic TSH in binding to receptors on thyroid membranes. Based on TSH receptor transfection studies, D2 and 4G11 show unequivocal specificity for the TSH receptor. To see if the complementary determining regions (CDRs) of these antibodies share any primary sequence similarities to regions of TSH critical for receptor binding, we deduced the primary structure of the variable regions of D2 and 4G11 by sequencing the immunoglobulin mRNA. We found that CDR1 of 4G11K and CDR2 of D2 mu show sequence similarity to regions of TSH alpha and TSH beta that had been previously implicated in the interaction of the hormone with its receptor. We tested the inhibitory effects of synthetic peptides from D2 mu-CDR2 and 4G11K-CDR1 on the binding of the corresponding antibodies to rat thyroid FRTL-5 cells and found an EC50 of 0.1 and 1 microM, respectively. TSH-derived peptides with similarity to D2 mu-CDR2 and 4G11K-CDR1 showed a significant but lesser effect on the binding of 4G11 or D2 to thyroid cells. Additionally, we tested the effects of the CDR peptides and TSH-derived peptides on TSH-stimulated cAMP production in FRTL-5 cells and found that D2 mu-CDR2 and 4G11K-CDR1 inhibited this activity, D2 mu-CDR2 most strongly (EC50 10 microM). Thus, linear sequences from the CDRs of these autoantiidiotypic antibodies with similarity to sequences from both subunits of TSH appear to interact with the TSH receptor. These data support previous studies indicating the complexity of the interaction between TSH and its receptor and advance earlier findings that such immunologic approaches are useful in dissecting receptor-ligand interactions.
1. Isolated hepatocytes from chicks were used to study the effects of pantethine supplementation to incubation medium on in vitro lipogenesis, CO2 production and beta-oxidation of fatty acid. 2. In vitro lipogenesis, determined by the incorporation of 1-[14C]acetate into total lipid and various lipid fractions, as depressed in concordance with the increase of pantethine concentration in the medium. 3. Incubation of isolated hepatocytes with pantethine resulted in a significant decrease (P < 0.01) in the activities of acetyl-CoA carboxylase and fatty acid synthetase. 4. The results suggest that in vitro fatty acid synthesis from 1-[14C]acetate was depressed and CO2 production was elevated in hepatocytes of chicks through pantethine addition to the medium at a low level.
In regenerating liver, a physiologically normal model of cell growth, LRF-1, JunB, c-Jun, and c-Fos among Jun/Fos/LRF-1 family members are induced posthepatectomy. In liver cells, high levels of c-Fos/c-Jun, c-Fos/JunB, LRF-1/c-Jun, and LRF-1/JunB complexes are present for several hours after the G0/G1 transition, and the relative level of LRF-1/JunB complexes increases during G1. We provide evidence for dramatic differences in promoter-specific activation by LRF-1- and c-Fos-containing complexes. LRF-1 in combination with either Jun protein strongly activates a cyclic AMP response element-containing promoter which c-Fos/Jun does not activate. LRF-1/c-Jun, c-Fos/c-Jun, and c-Fos/JunB activate specific AP-1 and ATF site-containing promoters, and in contrast, LRF-1/JunB potently represses c-Fos- and c-Jun-mediated activation of these promoters. Repression is dependent on a region in LRF-1 that includes amino acids 40 to 84 (domain R) and the basic/leucine zipper domain. As the relative level of LRF-1/JunB complexes increases posthepatectomy, c-Fos/Jun-mediated ATF and AP-1 site activation is likely to decrease with simultaneous transcriptional activation of the many liver-specific genes whose promoters contain cyclic AMP response element sites. Thus, through complex interactions among LRF-1, JunB, c-Jun, and c-Fos, control of delayed gene expression may be established for extended times during the G1 phase of hepatic growth.
The liver is one of the few adult tissues that has the capacity to regenerate following hepatectomy or toxic damage. In examining the early growth response during hepatic regeneration, we found that a highly induced immediate-early gene in regenerating liver encodes RL/IF-1 (regenerating liver inhibitory factor) and is the rat homolog of human MAD-3 and probably of chicken pp40. RL/IF-1 has I kappa B activity of broad specificity in that it inhibits the binding of p50-p65 NF-kappa B, c-Rel-p50, and RelB-p50, but not p50 homodimeric NF-kappa B, to kappa B sites. Like RL/IF-1, several members of the NF-kappa B and rel family of transcription factors are immediate-early genes in regenerating liver and mitogen-treated cells. We examined changes in kappa B site binding activity during liver regeneration and discovered a rapidly induced novel kappa B site-binding complex designated PHF [posthepatectomy factor(s)]. PHF is induced over 1,000-fold within minutes posthepatectomy in a protein synthesis-independent manner, with peak activity at 30 min, and is not induced by sham operation. PHF is distinct from p50-p65 NF-kappa B, which is present only in the inactive form in liver posthepatectomy. Although early PHF complexes do not interact strongly with anti-p50 antibodies, PHF complexes present later (3 to 5 h) posthepatectomy react strongly, suggesting that they contain a p50 NF-kappa B subunit. Unlike p50-p65 NF-kappa B, c-Rel-p50, and RelB-p50 complexes, PHF binding to kappa B sites is not inhibited by RL/IF-1. One role of RL/IF-1 in liver regeneration may be to inhibit p50-p65 NF-kappa B activity present in hepatic cells, allowing for the preferential binding of PHF to kappa B sites. Because PHF is induced immediately posthepatectomy in the absence of de novo protein synthesis, PHF could have a role in the regulation of liver-specific immediate-early genes in regenerating liver.
Cardiovocal syndrome is a rare clinical diagnosis that signifies vocal cord palsy associated with various cardiovascular diseases. The radiological manifestations of six cases of clinically diagnosed cardiovocal syndrome are reviewed retrospectively. The common clinical presentation of these six cases was hoarseness that was due to left vocal cord palsy. By means of chest X-rays (CXR) and cardioangiography, four cases were respectively diagnosed to have atrial septal defect (n = 1), ventricular septal defect (n = 1) and mitral stenosis (n = 2), all of which were associated with a common radiological finding of dilatation of pulmonary trunk. The other two cases were separately diagnosed to have proximal descending aortic saccular aneurysm (n = 1) by means of CXR and angiography, and fusiform ascending aortic aneurysm (n = 1) by computed tomography and magnetic resonance image. All these radiological presentations of either aortic aneurysm or dilated pulmonary trunk were associated with encroachment of aorticopulmonary window for which the left recurrent laryngeal nerve was presumably compressed with the result of left vocal cord palsy. Hoarseness that is caused by these underlying cardiovascular diseases is correctable after treatment of the underlying diseases. Hence, clinicians and radiologists should pay attention to the radiological manifestations of patients whose chief complaints are hoarseness and cardiovocal syndrome.
In six cases of acoustic neurilemmoma, electrocochleogram (ECOchG), brainstem auditory evoked potentials (BAEP) and facial muscle electromyograms (EMG) were recorded to monitor facial nerve and brainstem function. Under isoflurane and nitrous oxide anesthesia, we recorded ECOchG from the tympanic membrane, BAEP from the scalp needle, and facial muscle EMG from the mentalis muscle. During surgery, the body temperature was kept above 36.5 degrees C, and PaCO2 above 30 mmHg. In all cases, the peak N1 of ECOchG and wave I of BAEP had identical latencies throughout the monitoring period. The response was faster and the amplitude was higher in the ECOchG recordings. For calculation of the I-III or I-V interpeak latency of BAEP, the wave I of BAEP could be confirmed more quickly and precisely by the peak N1 of ECOchG. During tumor removal, the embedded facial nerve pathway in the tumor was identified by electric stimulation of the intracranial facial nerve, followed by evoked facial muscle EMG. Facial nerve function was confirmed by nerve traction or direct electric stimulation after total removal of the tumor. No facial palsy or other neurologic sequelae was found after the operations.
We reviewed the clinical results and radiographs of four patients who had revision of the acetabular component of a failed total hip arthroplasty with a bipolar socket supplemented by autoallograft to reconstruct massive bony defect. These patients were followed up from twelve to seventeen months. The clinical score was assessed by a modified d'Aubigne's rating score that assigned a maximum of 18 points. The preoperative clinical score ranged from 1 to 5 points (mean: 3.25 points). The postoperative score improved to a range of 13-17 points (mean: 15.25 points). Of the hips examined, nearly all were pain-free. The largest possible bipolar cup was used with solid structural allografting augmented by morseled cancellous autograft. These have been uniformly trouble-free with acetabular reconstitution. Cup migration was minimal or none. The follow-up periods were short and some migration is probably to be anticipated in the future. Although this technique was originally conceived as part of a staged procedure, it seemed as a definitive procedure yielding acceptable results for dealing with a severely deficient acetabulum. Larger series and longer periods of follow-up are demanded to support this assertion.
Bungarus multicinctus venom was incorporated into sphingomyelin-cholesterol liposomes which were stabilized with osmium tetroxide. The lethal toxicity of B. multicinctus venom in osmicated liposomes greatly decreased to 1.03% that of crude venom. Rabbits were divided into four groups for immunization. Group A was immunized with crude venom, group B and group C with osmicated liposomes, and group D with osmicated liposomes followed by the crude venom. Immunization was performed in the presence of Freund's adjuvant except for group B. The antibody levels during the course of immunization were measured by ELISA and the contents of precipitating antibody were determined by quantitative precipitin reactions, while that of non-precipitating antibody was determined by affinity chromatography. Although the immune response was not increased by incorporating lipopolysaccharide immunostimulant, the specific neutralizing capacity of purified antibody from the pooled antisera of group D was more potent than that of the others. The almost non-toxic osmicated liposomes of B. multicinctus venom may be useful immunogens for the production of antiserum for treatment of snake bites.
Liver regeneration provides one of the few systems for analysis of mitogenesis in the fully developed, intact animal. Several proteins have been identified as part of the primary growth response in regenerating liver and in mitogen-stimulated cells. Some of these proteins, such as the Jun and Fos families of transcription factors, are thought to have a role in activating transcription of genes expressed subsequently in the growth response. Through differential screening of a regenerating-liver cDNA library, we have identified a rapidly and highly induced gene encoding a 21-kDa leucine-zipper-containing protein that we have designated liver regeneration factor 1 (LRF-1). LRF-1 has no homology with other leucine-zipper proteins outside the basic and leucine-zipper domains. LRF-1 alone can bind DNA, but it preferentially forms heteromeric complexes with c-Jun and Jun-B and does not interact with c-Fos. In solution, it binds with highest affinity to cAMP response elements but also has affinity for related sites. In cotransfection studies, LRF-1 in combination with c-Jun strongly activates a c-Jun-responsive promoter. The induction of the LRF-1 gene in regenerating liver greatly increases the potential variety of heterodimeric combinations of leucine-zipper transcription factors. While LRF-1 mRNA is rapidly induced in the absence of protein synthesis, its peak induction is later than c-fos mRNA, suggesting that LRF-1 may regulate responsive genes at a later point in the cell cycle. As such, LRF-1 may have a unique and critical role in growth regulation of regenerating liver and mitogen-stimulated cells.
Liver regeneration provides a unique system for analysis of mitogenesis in intact, fully developed animals. Cellular immediate-early genes likely play an important role in cell cycle regulation and have been extensively studied in mitogen-stimulated fibroblasts lymphocytes but not in liver. We have begun to characterize the immediate-early growth response genes of mitogen-stimulated liver cells, specifically, regenerating liver and insulin-stimulated Reuber H-35 hepatoma cells, and to address differences in growth response between different cell types. Through subtraction and differential screening of cDNA libraries from regenerating liver and insulin-treated H-35 cells, we have extensively characterized 341 differentially expressed clones and identified 52 immediate-early genes. These genes have been partially sequenced and subjected to Northern (RNA) blot analysis, and 41 appear to be novel. Surprisingly, two-thirds of these genes are also expressed in BALB/c 3T3 cells, but only 10 were identified in previous studies of 3T3 cells, and of these, 6 include well-known genes like jun and fos, and only 4 are novel. Approximately one-third of the immediate-early genes identified in mitogen-stimulated liver cells or serum-stimulated NIH 3T3 cells are expressed in a tissue-specific fashion, indicating that cell type-specific regulation of the proliferative response occurs during the immediate-early period. Our findings indicate that the immediate-early response is unusually complex for the first step in a regulatory cascade, suggesting that multiple pathways must be activated. The abundance of immediate-early genes and the highly varied pattern of their expression in different cell types suggest that the tissue specificity of the proliferative response arises from the particular set of these genes expressed in a given tissue.
Fournier's gangrene is an acute gangrenous inflammation of the male genitalia. In an 18-month period, four patients with Fournier's gangrene were treated at our hospital. Their ages ranged from 39 to 74 years (average 55.2). The presenting symptoms and signs included pain, swelling and necrosis of the scrotum and perineum, fever and jaundice were also noted. Three patients with the predisposing factor of urinary tract infection or perianal abscess recovered after surgical debridement and antibiotics treatment. Their hospital stay ranged between 13 and 50 days. One patient with diabetes, presenting severe septic shock at arrival, died one day after debridement. From the experience of our cases and review of the literature, early surgical debridement and antibiotics are mandatory for the treatment of Fournier's gangrene.
In 1976, Jannetta et al, suggested that microvascular compression caused by arteries and veins crossing the root entry zone of the facial nerve, was the major etiology of hemifacial spasm (HFS). Surgical treatment has become a major trend. Microvascular decompression (MVD) with teflon patches has a high cure rate. However, the possible occurrence of multiple vessel compression makes it difficult to decide which of these vessels are responsible for the symptom during operation. Recently, a method of abnormal EMG was elaborated upon by Møller and Jannetta in 1987, to ensure the quality of MVD intraoperatively. In this study, we report 6 cases who underwent the procedure successfully. After general anesthesia and muscle relaxation, the abnormal EMG was not suppressed. When the offending vessel was lifted up from the facial nerve, the abnormal EMG disappeared immediately. In each case, postoperative improvement of facial spasm correlated with intraoperative abnormal EMG changes. This method is not only able to guide the surgeon to the vessel that induces HFS but also guarantees the quality of MVD.
We reviewed the computed tomographic (CT) findings of the sella turcica in 26 patients with a serum prolactin level of over 200 ng/ml. The interval between the dates of CT examination and checking of the serum prolactin level were within 2 months. There were 24 nonpregnant women with a mean age of 30 years and 2 men with a mean age of 28.5 years. None of them were taking medication known to cause an elevation in serum prolactin levels. Surgery was performed on 8 patients with chromophobe adenomas of the pituitary gland: 6 of them were proven to have prolactin-secreting tumors (prolactinomas) after performing a special stain, and the remaining 2 patients, clinically diagnosed as prolactinomas, showed extremely high serum prolactin levels (3,200 and 2,251 ng/ml, respectively). CT studies showed that the height of the pituitary gland in the coronal sections were more than 7 mm in 15 cases (58%) and more than 10 mm in 13 cases (50%); focal bulging of the diaphragma sellae in 16 cases (62%); erosion of the sellar floor in 20 cases (77%); deviation of the pituitary stalk in 19 cases (73%); and abnormal attenuation or enhancement of the pituitary gland in 18 cases (69%). Three patients (12%) showed no evidence of any abnormal CT finding despite a hyperprolactinemic state of over 200 ng/ml. Six histologically proven cases (23%) of prolactinomas and chromophobe adenomas showed radiologic evidence of cavernous sinus invasion. We conclude that patients with a serum prolactin level higher than 200 ng/ml generally show significant changes in the sella turcica in CT.
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Five patients with underlying malignancy were detected antemortemly to have cardiac metastasis by post-enhanced CT scanning. The most common presentations were abnormal heart sounds, electrocardiographic changes and inexplicable heart failure; which lead us to suspect cardiac metastasis. One patient had an "engorged azygous knob" on his chest x-ray film, which provided a clue to possible cardiac metastasis. All of these patients had tumor thrombi in their large tributary veins in addition to the primary tumors. Thus, we advanced the CT scan to the cardiac region and cardiac metastases were, therefore, diagnosed. The tumor thrombi in the large tributary veins seemed to be the source for intracardiac spreading. Cardiac angiographies were performed in 3 patients and confirmed the diagnosis. We conclude that post-enhanced CT scanning is useful in the diagnosis of cardiac metastasis and the presence of tumor thrombi in the large tributary vein is an early sign of cardiac involvement.