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Biomedical subjects

J C Lin

Publications and source records attributed to J C Lin.

At least 37 records · Page 2Linked to original sources

Inhibitory effects of acyclic nucleoside phosphonate analogs, including (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, on Epstein-Barr virus replication.

(S)-9-(3-Hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)-2,6-diaminopurine [(S)-HPMPDAP], cyclic (S)-HPMPA [(S)-cHPMPA], 9-(2-phosphonylmethoxyethoxyethyl)-2,6-diaminopurine (PMEDAP), and (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine [(S)-HPMPC] were examined for their inhibitory effects on Epstein-Barr virus (EBV) replication. The 50% effective concentrations for inhibition of viral DNA replication were 0.16, 0.03, 2.0, 1.5, and 0.08 microM for PMEDAP, (S)-HPMPC, (S)-HPMPDAP, (S)-cHPMPA, and (S)-HPMPA, respectively. The relative efficacies based on the in vitro therapeutic index was (S)-HPMPC (5,000) greater than PMEDAP (1,000) = (S)-HPMPA (1,000) greater than (S)-cHPMPA (136) greater than (S)-HPMPDAP (78). Certain ratios of combinations of (S)-HPMPC with 3'-azido-3'-deoxythymidine produced a synergistic inhibitory effect on EBV genome replication, but others exhibited an antagonistic effect. These results indicate that this series of acyclic nucleoside phosphonate analogs, and in particular (S)-HPMPC, are potent and selective anti-EBV agents in vitro.

Adenine

Expression of the Epstein-Barr virus BamHI A fragment in nasopharyngeal carcinoma: evidence for a viral protein expressed in vivo.

A family of mRNAs that are transcribed rightward through the BamHI A fragment have been detected in C15, a nasopharyngeal carcinoma (NPC) which has been passaged in nude mice. Northern (RNA) blot hybridizations indicate that these RNAs are also expressed in three other NPCs which have been established in nude mice and in an NPC obtained at biopsy. Moreover, hybridization in situ detected transcription from BamHI A in 12 NPCs and 1 Epstein-Barr virus (EBV)-containing carcinoma of the parotid gland. In each case, transcription was detected in all of the malignant epithelial cells. Transcription was not detected in two cases of EBV-positive lymphoma biopsies by in situ hybridization nor in latently infected EBV-positive lymphoblastoid cell lines by Northern blot hybridization. The consistent transcription of these sequences in latently infected epithelial malignancy but not in lymphoid cells suggests that this viral function is associated with latent EBV infection of epithelial cells. Sequence analysis of a cDNA synthesized from the C15 tumor, representing the 3' end of BamHI A messenger RNA, revealed an open reading frame (ORF). Translation of this ORF in vitro produced several peptides that were immunoprecipitated with antisera from patients with NPC. The detection of antibodies to the protein encoded by the ORF present in the BamHI A cDNA indicates that BamHI A encodes a protein which is expressed in vivo and is antigenic.

Animals

Identification and functional characterization of Epstein-Barr virus DNA polymerase by in vitro transcription-translation of a cloned gene.

In order to identify the gene encoding the Epstein-Barr virus (EBV) DNA polymerase, a portion of the BamHI-A fragment containing the fifth leftward open reading frame (BALF5) of the EBV genome was cloned into SP6 and T7 promoter-containing vectors for in vitro transcription-translation. The RNA synthesized in vitro was used to program rabbit reticulocyte lysates, which were analyzed for the synthesis of the putative polymerase polypeptide (110 kDa) and assayed directly for EBV DNA polymerase activity. The polypeptide synthesized by the full-length BALF5 genomic fragment had a molecular mass of 110 kDa. 5'-truncated BALF5 with the first and second ATGs deleted produced 95- and 83-kDa polypeptides, respectively. All three translation products were enzymatically active and displayed resistance to high salt concentrations. The identity of the largest polypeptide as the viral polymerase was established by (i) immunoprecipitation with EBV-positive sera from patients with nasopharyngeal carcinoma and by a rabbit polyclonal antiserum prepared with a synthetic peptide derived from the DNA sequence of BALF5; (ii) identification of a polypeptide of identical size (110 kDa) immunoprecipitated from superinfected Raji cell extracts by these antibodies; and (iii) salt-resistant enzymatic activity which was neutralized by the rabbit EBV antiserum. Thus, BALF5 encodes a functional polymerase identical to that induced in superinfected Raji cells.

Cell Line

Perspectives on health effects of electric and magnetic fields.

Some epidemiological studies have fostered concern about cancers caused by electric and magnetic fields associated with distribution and use of electric power. At present, there is no scientific consensus as to which factors, the electric field and/or magnetic field, are biologically important. Similarly, there is no clear indication whether higher field levels are of greater risk than lower level fields. The complex scientific issues attending health effects of power-frequency electric and magnetic fields would be most effectively resolved through interdisciplinary research involving investigators from biological, medical and engineering research communities. A critical need, at present, is a significant increase in federal funding for research on interaction mechanisms and animal studies, while maintaining efforts in epidemiology but with greater emphasis on confounding factors and known cancer-causing agents.

Animals

Renal osteodystrophy.

The term "renal osteodystrophy" is used to include skeletal disorders of patients with chronic renal failure: osteitis fibrosa, osteomalacia, osteosclerosis, osteoporosis and the frequently associated extraskeletal calcifications. It is the chronic glomerular disease with phosphate retention and resultant hyperphosphatemia on one hand and deficient 1,25 (OH)2 D3 and resultant hypocalcemia on the other to induce secondary hyperparathyroidism. The three most common causes of chronic renal failure in our patients are chronic glomerulonephritis, diabetic nephropathy, hypertensive nephropathy in decreasing frequency, polycystic renal disease occurs in five patients. Other miscellaneous causes include nephrotic syndrome, chronic pyelonephritis, systemic lupus erythematosus, periarteritis nodosa, interstitial nephritis and renal stones. The bone changes are similar in primary and secondary hyperparathyroidism and the incidence of brown tumor is about 3% in the former and 1.5 to 1.7% in the latter. We present one among the 94 dialyzed patients who has long-standing severe chronic renal failure from polycystic kidney disease and develops brown tumor in the mid ulna after 7 years on maintenance hemodialysis. The incidence of brown tumor in our series is about 1.1%. Because of increased longevity of the dialyzed patients, brown tumor from secondary hyperparathyroidism is now more commonly observed. Hyperphosphatemia with serum calcium-phosphate products exceeding plasma solubility of 60 to 75 mg/dl may induce soft tissue and vascular calcification. This explains the much higher incidence of soft tissue calcification in secondary than primary hyperparathyroidism; two of our patients with generalized Monckeberg's type arterial calcification and multiple periarticular calcifications in five patients have been observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

[Lennox-Gastaut syndrome with band form heterotopia: a case report].

A 10-year-old girl with developmental delay, mental retardation and intractable seizures is reported. She manifested clinically as Lennox-Gastaut syndrome with unknown etiology before admission. Brain MRI revealed a band-like lesion over the bilateral subcortical region being later recognized as band-form heterotopia. This type of heterotopia may be overlooked easily due to its symmetrical distribution and mild degree of cortical convolutional anomaly. As it is often associated with intractable seizures and psychomotor retardation, the prognosis is poor. This patient responded poor to ketogenic diet and anticonvulsants. We present this case and review the related articles.

Brain Neoplasms

Fournier's gangrene: experience of four cases.

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.

Adult

[Production and characterization of monoclonal antibody against colon cancer associated antigen in Chinese].

Although many monoclonal antibodies have been made in human colon cancer, none of them are from the Chinese species. Recently, a colon cancer cell line CC-M2 established from a Chinese patient has been completely characterized and used as immunogen to produce monoclonal antibodies. Monoclonal antibodies were produced by standard hybridoma technique. The fusion rate was 95.8%. An isotype IgG1 of high proliferation named as Sam-2 was used in this study. The titers were measured around 10(4). Further studies on MoAb Sam-2 through indirect immunofluorescent and immunoperoxidase tests revealed its good specificity and sensitivity in colorectal cancer tissue. In CEA study, the result indicated that Sam-2 may react on a non-CEA related antigen. For further clinical application, the antigen was identified as a glycoprotein by chemical resistant test. In preliminary studies using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting techniques, Sam-2 could recognize two closed antigens or a dimer antigen with molecular weight 25.2 and 27 Kd respectively.

Animals

Changes in intratumor pH by two heatings.

It is a known fact that pH in rodent tumors decline significantly upon heating most likely due to breakdown of the tumor blood circulation. We recently observed that tumor blood vessels become thermotolerant after being heated with a sublethal thermal dose. The purpose of the present study was to reveal whether heating can reduce intratumor pH when the tumor vessels are thermotolerant. When the SCK tumors of A/J mice were heated at 42.5 degrees C for 1 h, the tumor vessels became most thermotolerant at 18 h postheating, as measured with the 86Rb uptake method. The intratumor pH in the control SCK tumors was 7.05 +/- 0.14 (SD), and it significantly decreased to 6.70 +/- 0.08 (P less than 0.001) after heating at 44.5 degrees C for 1 h. However, when the tumor vessels were thermotolerant, i.e., 18 h after heating at 42.5 degrees C for 1 h, reheating at 44.5 degrees C for 1 h could not reduce the intratumor pH. We concluded that such a failure to increase tumor acidity by a second heating at temperatures as high as 44.5 degrees C was due to vascular thermotolerance developed by the first heating.

Animals

Characterization of four newly established human colorectal adenocarcinoma cell lines from Chinese patients.

Four colon adenocarcinoma cell lines, CC-M2, CC-M3, CC-M4, and CC-M2NM, have been established from surgical specimens of 18 unselected patients without the use of "feeder" cells and additional growth factors (e.g., insulin, hydrocortisone, etc.) in the culture medium. The methods of primary cultivation of tissue explants are described. Studies of determination of morphology, growth curve, plating efficiency, chromosomal analysis, CEA and beta-HCG synthesis, and tumorigenicity, were done to characterize the cell lines. Significant variations have been found in one of the four cell lines, both in vitro and in vivo studies. There are distinct phenotypes in the established cell lines which may be useful in studying the cell differentiation and progression of colorectal cancer.

Adenocarcinoma

Extralobar pulmonary sequestration of the left retroperitoneum.

This paper presents an extralobar pulmonary sequestration in the left retroperitoneum in an eight year old girl. The clinical and diagnostic features included abdominal pain, an abdominal mass, elevated VMA, and radiological manifestations simulating a left adrenal mass. A laparatomy was performed. Extralobar pulmonary sequestration of the left retroperitoneum is fairly uncommon. An eight year old girl was admitted with abdominal pain, elevated urinary VMA and an abdominal mass. The radiological manifestations simulated a left adrenal mass. At surgery an extralobar pulmonary sequestration was detected.

Bronchopulmonary Sequestration

Cancer of the auricle.

Thirty-five patients with carcinoma of the auricle seen in Veterans General Hospitals, Taipei and Taichung from January 1970 to December 1988 were reviewed retrospectively. There were 28 men and 7 women. More cases occurred in the 7th and 8th decades with an average of 64 years (median 67) and ranged from 29 to 91 years. The most common manifestations at diagnosis were exophytic mass (86%) and/or ulcerative lesion (29%). Histologically, basal cell carcinoma outnumbered squamous cell carcinoma 17 to 14. The remaining 4 cases consisted of 2 melanomas, 1 sweat gland adenocarcinoma and 1 unclassified sarcoma. Eighty-eight percent (15/17) of basal cell carcinoma presented at early stage without regional lymph node or distant metastasis. They were mainly treated by surgery. One patient with multifocal lesions suffered from marginal recurrence. The 2 and 5-year survival rates were 94% and 86% respectively. Half of our 14 patients with squamous cell carcinoma had local extensive tumor but no lymph node or distant metastasis was found at the time of diagnosis. Local recurrence occurred in 4 patients, one case associated with lung metastasis. The local control rate of combined surgery and irradiation in squamous cell carcinoma was 100% (4/4), superior than that of operation alone 67% (6/9) or radiotherapy alone (0/1). The actual 2 and 5-year survival rates were 85% and 64% respectively. Our 4 patients with different pathology other than basal cell or squamous cell carcinoma had high rate of regional lymph nodes or distant metastases, presenting poor prognosis. The overall treatment failure for carcinoma of the auricle was 23% (8/35) but reduced to 14% after salvage treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Perianal Paget's disease--report of 4 cases.

Over the past nine years (from 1981 to 1989), four patients with perianal Paget's disease were treated. All were male with an average age of 58.5 years. Clinically, perianal Paget's disease manifests as a slowly enlarging eczematous, and sharply demarcated perianal skin rash that may be oozing or itching. In the characteristic pathology finding, Paget's cells appear as large, rounded signet-ring cells with abundant mucin stain positive cytoplasm in the basal layer of the acanthotic epidermis. All but one, who suffered from primary sweat gland carcinoma, had underlying rectal adenocarcinoma. The first two cases expired soon after a delayed diagnosis of terminal underlying malignancy. Only in the later two cases was there a preoperative suspicion of perianal Paget's disease. There is often a delay in diagnosis due to clinical ignorance. Patients with persisting perianal skin rash should be biopsied frequently. If perianal Paget's disease is diagnosed, the underlying malignancy should be surveyed and managed thoroughly.

Aged

Effects of hydralazine on the blood flow in RIF-1 tumors and normal tissues of mice.

Hydralazine is a peripheral vasodilator used as an antihypertensive agent. Hydralazine has been reported to potentiate tumor damage by hyperthermia as well as by hypoxic-cell-specific drugs through the reduction of tumor blood flow and pO2. In the present study, we investigated the changes in blood perfusion caused by hydralazine in S.C. RIF-1 tumors and normal tissues in C3H mice using the 86Rb uptake technique and laser Doppler flowmetry. The tumor blood flow was decreased significantly by an intravenous administration of 0.5-10.0 mg/kg hydralazine, as determined by both uptake of 86Rb and laser Doppler flowmetry. The tumor pO2 was also decreased significantly by the injection of hydralazine. On the other hand, the uptake of 86Rb was increased significantly in the skin and muscle by hydralazine. The changes seen in the skin and muscle after injection of hydralazine as assessed by laser Doppler flowmetry were similar to those assessed by uptake of 86Rb, indicating a significant increase in blood circulation in these tissues. Uptake of 86Rb remained unchanged in the kidney and decreased in the liver and spleen in the presence of hydralazine in a dose-dependent manner at 0.5-10.0 mg/kg. The decline in uptake of 86Rb in normal tissues strongly suggests that hydralazine decreases the blood flow in these normal tissues. Thus the recent proposal to use hydralazine to increase the antitumor activity of heat or certain drugs needs to be reexamined.

Animals

The kinetics of vascular thermotolerance in SCK tumors of A/J mice.

Development of thermotolerance has been observed in diverse biological systems. Despite the important role of blood circulation in heat-induced tissue damage, little is known about vascular thermotolerance. The kinetics of vascular thermotolerance in SCK tumors of A/J mice was investigated in this study. A single heating at 43.5 degrees C or 44.5 degrees C for 1 hr caused marked damage in tumor vasculature, as demonstrated by a marked decrease in Rb-86 uptake (% of injected dose/g of dried tissue). The tumor vasculature became resistant or tolerant to subsequent heatings at those temperatures when the tumors were preheated at 42.5 degrees C for 1 hr. Vascular thermotolerance became significant at 5 hr and reached its maximum at 18 hr after preheating at 42.5 degrees C. When the vascular thermotolerance was at its peak, heating at temperatures as high as 44.5 degrees C for 1 hr could not reduce the tumor blood flow. The vascular thermotolerance decayed considerably but not completely at 72 hr after the preheating. The vascular thermotolerance may exert a profound implication on the response of tissues, including tumors, to multiple heatings.

Adaptation, Physiological

Synergistic inhibition of Epstein-Barr virus: transformation of B lymphocytes by alpha and gamma interferon and by 3'-azido-3'-deoxythymidine.

We analyzed the effects of 3'-azido-3'deoxythymidine (AZT) and alpha and gamma interferon (IFN-alpha and IFN-gamma) on transformation of human umbilical cord lymphocytes (HUCLs) by Epstein-Barr virus (EBV). B lymphocytic outgrowth from HUCLs infected with EBV was monitored by focus formation; the presence of EBV genomes in transformed foci was confirmed by in situ cytohybridization and EBV nuclear antigen. The 50% inhibitory doses for preventing focus formation were 0.14 microM for AZT, 10 units (U)/mL for IFN-alpha, and 1 U/mL for IFN-gamma. To determine whether inhibition resulted from direct cytotoxic effects, we assessed the viability of nontransformed HUCLs exposed to the agents for 30 d. The nontoxic doses were 1 microM for AZT, 30 U/mL for IFN-alpha, and 3 U/mL for IFN-gamma. Combining IFN-alpha or IFN-gamma with AZT or IFN-alpha with IFN-gamma at nontoxic doses showed synergistic decreases in numbers of transformed foci. Transformation of HUCLs by EBV was sensitive to, but not abolished by, these agents at doses below those required for cell killing.

B-Lymphocytes

Reversal by glucose of pancreatic amylase insufficiency in chronic alcoholic rats.

Carbohydrate consumption regulates pancreatic amylase synthesis in rats. The Lieber-DeCarli 36% alcohol diet employed in chronic alcohol studies and the isocaloric control diet contain 11 and 47% of total calories from carbohydrates, respectively. Young rats fed ad libitum the 36% ethanol diet for 2 weeks obtained 1.2 g/day of carbohydrate, whereas those pair-fed with control diet received 5.8 g/day. Rats fed the 36% ethanol diet and given an intramuscular injection of a solution of 1.5 g of glucose daily for 2 weeks received twofold greater amounts of carbohydrate than saline-injected controls (2.7 versus 1.2 g). These changes in carbohydrate intake produced proportionate changes in pancreatic amylase levels. The secretory responses to cholecystokinin-octapeptide (CCK8) of acini from control and glucose-injected rats were significantly higher compared with those in the saline-injected or noninjected alcohol groups. The blood alcohol levels in glucose-injected rats were markedly reduced compared with other alcohol groups (71.7 versus 274.9 mg/dl) despite similar amounts of ethanol ingestion daily (2.4 g) in the three groups. In vitro experiments with acini from rats fed a nutritionally optimal diet revealed that high pharmacologic concentrations of ethanol, while inducing basal secretion, inhibited CCK8-stimulated amylase secretion. These results indicate that: (a) the amount of alcohol consumption does not correlate with either the levels of blood alcohol or of pancreatic amylase; (b) the carbohydrate availability in rats regulates pancreatic amylase levels despite significant levels of alcohol in blood; (c) blood alcohol levels observed in vivo may not affect synthetic and secretory processes of amylase in pancreatic acini.

Alcoholism

Regulation of pancreatic amylase by dietary carbohydrate in chronic alcoholic rats.

The nutritional adequacy of dietary ingredients is essential for optimal food consumption and growth of animals. Dietary carbohydrate levels regulate pancreatic amylase synthesis. Ethanol diets with 36% of total calories from ethanol and 11% from carbohydrate are nutritionally inadequate, whereas a 26% ethanol diet made isocaloric to the 36% alcohol diet by the addition of maltose-dextrins provides all nutrients in amounts recommended for normal growth. Young rats fed the modified ethanol diet for 3 months consume 101.4 ml of diet daily compared to 66.5 ml by those on the 36% ethanol diet. Increased food consumption results in (a) similar amounts of alcohol consumption (3.6 vs. 3.3 g/day), (b) a threefold enhancement in carbohydrate intake (5.1 vs. 1.7 g/day), and (c) a normal growth rate (6.7 vs. 3.1 g/day). Both the acinar content of amylase (20.2 +/- 0.3 micrograms/mg of protein) and the acinar response to cholecystokinin-octapeptide in 36% ethanol diet-fed rats are significantly reduced compared to those of 26% ethanol diet-fed rats (34.1 +/- 5.6 micrograms/mg of protein). These results confirm (a) the nutritional adequacy of the 26% ethanol diet compared to the 36% ethanol diet, and (b) that carbohydrate inadequacy, and not ethanol consumption per se, is the primary cause of pancreatic amylase insufficiency in chronic alcoholic rats.

Alcoholism