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Biomedical subjects

H S Lin

Publications and source records attributed to H S Lin.

At least 55 records · Page 3Linked to original sources

Radiation therapy for primary orbital lymphoma.

PURPOSE: The influence of tumor size, grade, thoroughness of staging workup, and radiation dose on disease control, radiation-related complications, and incidence of systemic progression of primary orbital lymphoma is analyzed. METHODS AND MATERIALS: Twenty patients with Stage I primary orbital lymphoma were treated from August 1976 through August 1991 at Mallinckrodt Institute of Radiology. Staging workups included physical examination, chest x-ray, complete blood count (CBC), liver function test, and computerized tomography (CT) scan of the orbit, abdomen, and pelvis. Nineteen patients had bone marrow biopsy. The histological types based on the National Cancer Institute working formulation were 9 low-grade and 11 intermediate-grade, including five lymphocytic lymphomas of intermediate differentiation. The extension of disease and the volume of tumor were evaluated by CT scan of the orbit. The most commonly used radiation therapy technique was single anterior direct field with 4 MV or 6 MV photons. Lens was shielded or not treated in eight patients. Dose ranged from 20 to 43.2 Gy. Thirteen of 20 patients received 30 Gy. Minimum follow-up was 24 months (median, 4 years). RESULTS: Local control was achieved in all 20 patients. One patient with lymphocytic lymphoma with intermediate differentiation developed disseminated disease. Actuarial disease-free survival (DFS) was 100% and 90% at 2 and 5 years, respectively. No retinopathy was observed. Cataracts were noted in seven patients at 1 to 10 years following irradiation (median, 2 years). Three patients developed lacrimal function disorder; however, no corneal ulceration occurred. CONCLUSIONS: Thirty Gy in 15 fractions appears to be a sufficient dose for local control with acceptable morbidity, especially for low-grade, as well as certain types of intermediate-grade lymphomas, such as diffuse small cleaved cell and lymphocytic lymphoma of intermediate differentiation. Systemic dissemination is minimal, provided local control is achieved and initial staging workups are adequate.

Adult↗

Synthesis and biological evaluation of a new series of sterols as potential hypocholesterolemic agents.

A new series of sterols was synthesized and tested in a CHO cell-based LDL receptor/luciferase (LDLR/Luc) assay to investigate the capability of derepressing the transcription of LDL receptor promoter in the presence of 25-hydroxycholesterol. The effect of various substitutions on antagonizing the repressing effect mediated by 25-hydroxycholesterol was also studied in terms of regio- and stereochemistry, lipophilicity, steric bulk, and pi-electron density. Except 12, compounds active in the primary LDLR/Luc assay were not active in the secondary simian virus 40/luciferase (SV40/Luc) assay, demonstrating the specificity of their in vitro activity. Eight active compounds of various structural types were selected and screened in a [1-14C-acetate]cholesterol biosynthesis inhibition assay; none has shown any interference with the cholesterol biosynthesis in CHO cells. In hypercholesterolemic hamsters, generally, compounds that were active in vitro were active in vivo and vice versa, with the exception of three in vitro inactive compounds: 3 beta-ols 3a' and 3c' as well as 3-ketone 2a. Experimental results from the livers of hamsters revealed that the in vivo conversion of 3a' or 2a to 3a has in part contributed to the observed in vivo activity, and it is also anticipated that 3c' may similarly be converted to 3c in hamsters.

Animals↗

Ultrastructural studies on macromolecular permeability in relation to endothelial cell turnover.

Our previous light microscopic studies demonstrated the correlation of focal arterial uptake of macromolecules with the mitosis or death of endothelial cells (ECs). To investigate horseradish peroxidase (HRP) permeability associated with the clefts surrounding these ECs at the ultrastructural level, experiments were performed on rat thoracic aortae by using transmission electron microscopy. In en face preparations of aortic specimens, light microscopy was used first to detect mitotic ECs by hematoxylin staining prior to electron microscopy. Dying (or dead) ECs containing cytoplasmic immunoglobulin G (IgG) were identified by an indirect immunogold technique, HRP was found to permeate from the vessel lumen through the widened junctions around the mitotic and dying cells, as well as some non-widened junctions and the plasma membrane of dying cells. The transiently open junctions during cell turnover lead to an increased transendothelial permeability to macromolecules. In addition to its enhanced passage through the leaky junctions around EC turnover and through the damaged membrane of dying cells. HRP can also traverse many normal intercellular clefts into the subendothelial space of the aorta. These observations show that normal intercellular junctions can provide a significant pathway for the transport of macromolecules with the size of HRP, and that HRP transport is enhanced in transiently open junctions surrounding ECs undergoing turnover. The widened junctions around the mitotic and dying cells provide the pathway for macromolecules larger than HRP, e.g., the low density lipoproteins (LDLs).

Animals↗

Adaptation and cross-resistance: an explanation for the existence of different radiosensitivities among malignant melanoma cells.

A hypothesis is presented to explain the apparent difference in the radioresponsiveness of melanoma lesions whether they are located on the skin or in other parts of the body. The hypothesis states that the radiosensitivity of a cell may change when the cell adapts to live and grow in a different environment. The most important environmental factor that affects the radiosensitivity of cutaneous melanoma cells appears to be the partial pressure of oxygen in their immediate environment. By virtue of adapting to grow in an environment having a high partial pressure of oxygen, the melanoma cells located on the skin may have developed a better antioxidant defense mechanism than cells that metastasize to, and grow in, other parts of the body having lower partial pressures of oxygen such as lymph nodes, brain and viscera. Because some of the cell-damaging effects of both oxygen and ionizing radiation are mediated through a similar mechanism, the melanoma cells on the skin become cross-resistant to ionizing radiation because of their higher tolerance to oxygen toxicity.

Adaptation, Physiological↗

Vitamin E succinate potentiates the inhibitory effect of prostaglandins on oral squamous carcinoma cell proliferation.

Previous studies have shown that prostaglandin E2 (PGE2) and vitamin E succinate can act in an additive manner to inhibit the proliferation of human oral squamous carcinoma cells (SCC-25). The initial studies on the additive anticancer activity of PGE2 and vitamin E succinate have been extended to include antineoplastic PGs, delta 12-PGJ2 and PGJ2. Treatment of oral squamous carcinoma cells (SCC-15) with delta 12-PGJ2, PGJ2, and vitamin E succinate, individually, caused significant concentration-dependent inhibition of cell proliferation to various degrees. PGJ2 was most potent and caused an inhibition that corresponded to 85.55% at 10(-5) M. Addition of 1 microM of vitamin E succinate to delta 12-PGJ2 or PGJ2 resulted in a significant increase in the inhibitory potency of the lower concentrations of the two PGs. These results suggest a novel role for a mixture of PGs and vitamin E as potent antitumor proliferative agents.

Antineoplastic Agents↗

Loss of alveolar macrophages during anesthesia and operation in humans.

Pulmonary macrophages play an important role in the host defense against infection, and the importance of this role is probably enhanced when the upper airway defenses are circumvented by endotracheal intubation. Studies in animals suggest that exposure to volatile anesthetics compromises the viability and function of alveolar macrophages. We studied the effect of surgery and anesthesia on the alveolar macrophages of 41 human subjects undergoing lower abdominal procedures of varying lengths during nitrous oxide-isoflurane anesthesia. Alveolar macrophages were harvested from bronchoalveolar lavage fluid obtained before incision and compared to those recovered just before emergence from anesthesia. Macrophages were analyzed for aggregation and viability, assessed by the ability of viable cells to exclude trypan blue dye. Operations lasting 2 h or less led to little aggregation and had little effect on viability. However, there was a strong correlation between loss of macrophages and the duration of surgery and anesthesia. Aggregation increased and viability decreased as a function of procedure length. Studies are needed to determine whether prolonged surgery contributes to the incidence of postoperative pulmonary complications by disturbing the function and survival of alveolar macrophages in humans.

Adolescent↗

Rapid determination of double bond configuration and position along the hydrocarbon chain in cyclic fatty acid monomers.

This study reports the structural elucidation of diunsaturated 5- or 6-membered ring cyclic fatty acid monomers (CFAM) isolated from heated flaxseed oil by complementary gas chromatography (GC)-mass spectrometry (MS) and GC-matrix isolation-Fourier transform infrared spectroscopy (MI-FTIR). Infrared measurements of CFAM were carried out on methyl ester derivatives as well-resolved chromatograms were obtained on a polar 100% cyanopropyl polysiloxane capillary GC column. By contrast, electron ionization MS of methyl ester derivatives was of limited value because of double bond migration during the ionization process in the mass spectrometer. This communication reports definitive MS fragmentation patterns that can confirm ring position and double bond position along the fatty acid chain in 1,2-disubstituted CFAM determined as 2-alkenyl-4,4-dimethyl-oxazoline derivatives. Double bond configuration (cis, trans, or conjugated cis,cis) in CFAM was confirmed by GC-MI-FTIR. The presence of CFAM, degradation products found in used frying oils, is a potential source of dietary toxicity.

Fatty Acids, Unsaturated↗

Permeability of the pineal organ of the golden hamster (Mesocricetus auratus) to HRP with special reference to different types of blood capillaries.

The pineal organ of the golden hamster consists of deep and superficial portions which are connected to each other by a stalk. The permeability of capillaries for horseradish peroxidase (HRP) injected intravenously was examined in sections of entire portions of the gland that cut either along coronal or sagittal planes. Two distinct portions of the parenchyma, i.e., dorsal major and ventral minor ones, were found in the superficial gland. Most of the capillaries in the dorsal portion were of the continuous type of endothelium, whereas those in the ventral portion were fenestrated. In the dorsal portion, HRP readily crossed the endothelium, permeated the basal lamina, flowed into the perivascular connective tissue space and intruded into the intercellular clefts of the parenchyma. In contrast, HRP was not found to penetrate through the endothelium of the capillaries in the ventral portion to reach the perivascular area, thereby leaving the intercellular clefts of the parenchyma free of HRP. In the deep gland the capillaries were exclusively of the nonfenestrated type. Intravenously injected HRP was prevented from crossing the endothelium by the tight junction. In some areas, HRP penetrated through the capillaries in the pia mater, and crossed the outer limiting membrane to reach the intercellular clefts of the parenchyma and the basal lamina of the capillaries in the peripheral region of the deep pineal gland. The junctions between endothelial cells were not penetrated by HRP. The observations indicate that the type of capillary, absence of perivascular spaces, and permeability in the deep pineal are all similar to these factors in the general brain tissue; they differ from these in the superficial pineal gland, in which the dorsal portion shows characteristics found in other endocrine glands, but the ventral zone exhibits a unique situations: the presence of a blood-pineal barrier with a pericapillary connective tissue area.

Animals↗

Bowel perforation--a fatal complication following renal transplantation: a report of two cases.

From May 1983 to January 1993, 162 patients received renal transplantation at Taichung Veterans General Hospital. Two patients developed bowel perforation after this surgery. One was proved at 21 days and another, at 13 days after renal transplantation. Both patients died as a direct result of the perforation. From a review of literature, the average incidence is 2.7%, and the average mortality rate is 56.5%. Because of this high mortality rate, a high clinical suspicion, prompt and adequate surgical intervention, reduction of immunosuppressive agents and effective antibiotic coverage should contribute to a decline in mortality.

Adult↗

Cytoplasmic pH influences cytoplasmic calcium in MC3T3-E1 osteoblast cells.

We found that the cytoplasmic concentration of calcium (Cai) of MC3T3-E1 osteoblasts was influenced by the type of pH buffer we used in the perfusing medium, suggesting that intracellular pH (pHi) might influence Cai. To study this effect, the Cai and pHi were monitored as we applied various experimental conditions known to change pHi. Exposure to NH4Cl caused a transient increase in both pHi and Cai without a change in extracellular pH (pHo). Decreasing pHo and pHi by lowering the bicarbonate concentration of the medium decreased Cai, and increasing pHi by the removal of 5% CO2 increased Cai. Clamping pHi to known values with 10 microM nigericin, a potassium proton ionophore, also influenced Cai: acid pHi lowered Cai, whereas alkaline pHi increased it. The rise in Cai appears to be very sensitive to the extracellular concentration of calcium, suggesting the existence of a pH-sensitive calcium influx mechanism. We conclude that physiologic changes in pH could modulate Cai by controlling the influx of calcium ions and could change the time course of the Cai transient associated with hormonal activation.

3T3 Cells↗

Prostaglandin E2 antagonizes gingival fibroblast proliferation stimulated by interleukin-1 beta.

Treatment of human gingival fibroblasts with prostaglandin E2 (PGE2) resulted in significant concentration-dependent inhibition in deoxyribonucleic acid (DNA) synthesis (8.40-37.89%), while indomethacin (INDO) (PG inhibitor), interleukin-1 beta (IL-1 beta) or IL-1 beta+INDO caused a significant and dose-dependent increase in DNA synthesis. Addition of PGE2 to culture media containing IL-1 beta and INDO caused a significant concentration-dependent reduction in IL-1 beta- and INDO-induced stimulation of DNA synthesis. The findings suggest that IL-1 beta and PGE2, which are also produced by fibroblasts, could play an important role in regulation of gingival tissue development and wound healing, and their modulation may have therapeutic potential.

Adult↗

Inhibition of human oral squamous carcinoma cell (SCC-25) proliferation by prostaglandin E2 and vitamin E succinate.

The primary objective of this investigation was to study the effect of D-alpha-tocopherol acid succinate (vitamin E succinate) and prostaglandin E2 (PGE2), individually and in combination, on the proliferation of human tongue squamous carcinoma cells (SCC-25) in vitro. Test compounds in varying concentrations were incubated with cells in serum-free Dulbecco's Modified Eagle's Medium-Ham's F-12 Medium (50:50), supplemented with 0.1% albumin for sixteen hours. Cell proliferation was measured by the incorporation of [3H] thymidine in acid-insoluble material (i.e. DNA). Prostaglandin E2 and vitamin E succinate, individually at 10(-9)-10(-6) M, caused significant dose-dependent inhibition in DNA synthesis. A combined dose of each compound at 10(-5) M resulted in significant additive inhibition which averaged 43.53% (p < 0.005). Addition of indomethacin (INDO) to cell cultures induced significant dose-dependent stimulation in DNA synthesis. Hence, we might suggest that the overall potential of vitamin E in controlling malignant cell proliferation in vivo could be due to its own effect combined with that of endogenous PGs which are normally produced in excessive amounts by malignant cells.

Carcinoma, Squamous Cell↗

Laurence-Moon-Biedl syndrome: report of two cases.

The Laurence-Moon-Biedl syndrome is characterized by features of familial occurrence, retinitis pigmentosa, obesity, polydactyly, hypogenitalism and mental retardation. Recently, several reports have suggested renal abnormalities as an additional cardinal feature of the syndrome. We present two cases of this syndrome from two different families. The first case was an obese eight-year-old girl with poor vision and signs of mental retardation beginning at four months of age. An intravenous urogram showed dilatation of the minor calyces of both kidneys. Genital agenesis and typical retinitis pigmentosa on fundal examination all supported the diagnosis of Laurence-Moon-Biedl syndrome. The patient's father and grandmother also had symptoms of poor vision, mental retardation and obesity. The second case was an obese 14-year-old girl with blurred vision and severe mental retardation noticed at two to three months of age. Fundi showed typical retinitis pigmentosa. She also had genital agenesis but no significant family history.

Adolescent↗

Nonpeptide angiotensin II receptor antagonists: synthetic and computational chemistry of N-[[4-[2-(2H-tetrazol-5-yl)-1-cycloalken-1- yl]phenyl]methyl]imidazole derivatives and their in vitro activity.

A series of nonpeptide angiotensin II receptor antagonists was synthesized and tested in vitro to investigate requirements for recognition by and binding to AT1 receptors. Compared to a known series of N-(biphenylylmethyl)imidazoles, including losartan (DuP 753), which has a more rigid conformation in the 2'-tetrazolylbiphenyl moiety, the new series replaces the terminal phenyl with cycloalkenyls. Compounds were made with five- to seven-membered rings and with either a hydroxymethyl (3) or carboxyl (4) group at the 5 position on the imidazole ring. The effects of the lipophilicity and steric bulk of the terminal ring system, the amount of pi-electron density in the terminal ring, and the relative spatial proximity of the tetrazolyl and the middle phenyl are explored in terms of binding affinity to AT1 receptors in rat adrenal glomerulosa and rabbit aorta. The physicochemical variables of the new compounds were quantitated by computational chemistry and compared to those of losartan and its carboxyl metabolite. Potency at the AT1 receptors is maximized when the terminal ring is six-membered; an aromatic ring binds better than a cycloalkenyl ring. The 5-carboxyimidazole compounds show higher affinity than the 5-hydroxymethyl series.

Angiotensin Receptor Antagonists↗

Primary listerial infections are exacerbated in mice administered neutralizing antibody to macrophage colony-stimulating factor.

The serum and tissue levels of macrophage colony-stimulating factor (M-CSF) are elevated in mice during a primary immunologic response to infection by Listeria monocytogenes. Experiments were performed to determine the specific role of M-CSF in the resolution of listerial infections. The bulk of Listeria injected into a mouse i.v. is deposited in the liver. The expression of M-CSF mRNA in the liver increased markedly within 2 h postinfection. Maximum expression was dependent upon the dose of Listeria inoculated. The administration of anti-M-CSF mAb reduced the percentage of Mac-1+ mononuclear phagocytes subsequently found in the livers of infected animals. This reduction correlated inversely with an increase in the number of Listeria associated with both the parenchymal and NPC populations. These results suggest that M-CSF may play an important role in the primary immunologic response to Listeria in the liver by stimulating the production, mobilization, and/or biologic activity of Mac-1+ mononuclear phagocytes.

Animals↗

Effect of vitamin C and vitamin E on prostaglandin synthesis by fibroblasts and squamous carcinoma cells.

Dietary levels of vitamins C and E have been associated with cancer prevention and to a lesser extent with therapeutic enhancement of cancer treatment. Inhibition of prostaglandins (PGs) by pharmacological agents has been demonstrated to enhance immunocompetence, and to suppress growth of tumors in animals and humans. We report here on the effect of vitamins C and E on PGE2 production by human gingival fibroblasts and SCC-25 oral squamous carcinoma cells. The results indicate: 1. vitamins C and E exert a dose-dependent effect on arachidonic acid (AA) release and PGE2 synthesis; 2. vitamin E has a biphasic effect which is stimulatory at 1 and 10 microM and inhibitory at 100 microM; 3. vitamin E is considerably more potent than vitamin C in its inhibitory effect on AA and PGE2 in both cell types; 4. a combination of the two vitamins has a consistent dose-dependent inhibitory effect on AA and PGE2; 5. vitamin C stimulates PGE2 synthesis from exogenous AA in fibroblasts, and inhibits it in SCC-25 cells. The in vivo significance of these findings requires further investigation.

Adult↗

Effects of light deprivation on prolactin cells in golden hamsters: an immunoelectron microscopic study.

In the golden hamster light deprivation has been shown to induce gonadal regression and reduction of pituitary and plasma levels of prolactin (PRL). In the present study we examined changes in morphology and population ratios of three types of PRL cells 8 weeks after light deprivation, by means of blinding or exposure of hamsters to continuous darkness. In the pituitary of intact hamsters of either sex, which were entrained to a 14-h light: 10-h dark cycle, Type C cells with large secretory granules were the most numerous and Type A with smaller granules the least. After light deprivation the pituitary was found to contain remarkably atrophic PRL cells and showed a profound change in population ratio of PRL cell types, i.e., Type A cells prevailed over the other two types. Pituitary glands from light-deprived and concurrently pinealectomized hamsters exhibited structures and a population ratio of three types of PRL cells similar to those from intact animals. It is suggested that small-granule-containing PRL cells represent an inactive stage of PRL cells, whereas medium- and large-granule-containing cells are functionally active cells. The atrophy of PRL cells can account for the decreased pituitary level of PRL in light-deprived hamsters reported previously.

Animals↗