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Biomedical subjects

H Lin

Publications and source records attributed to H Lin.

At least 361 records · Page 20Linked to original sources

Fusome asymmetry and oocyte determination in Drosophila.

Germline cysts containing 16 interconnected cells (cystocytes) are produced at an early stage of Drosophila oogenesis by progenitor cells known as cystoblasts that undergo four synchronous rounds of incomplete division. During cyst formation, a region of specialized, spectrin-rich cytoplasm called the fusome traverses the intercellular connections (ring canals), linking individual cystocytes. Subsequently, 15 cystocytes begin to transport specific RNAs and other components into the remaining cell, the future oocyte. We used fusome-specific antibodies to characterize the early stages of cyst formation. During the first cystoblast division, a spherical mass of fusome material (the "spectrosome") was associated with only one pole of the mitotic spindle, revealing that this division is asymmetric. During the subsequent three divisions, the growing fusome always associated with the pole of each mitotic spindle that remained in the mother cell, and only extended through the newly formed ring canals after each division was completed. These observations suggest that fusomes help establish a system of directional transport between cystocytes that underlies oocyte determination.

Animals↗

Tumor necrosis factor-alpha and interferon-gamma modulation of nitric oxide and allograft survival.

Tumor necrosis factor-alpha (TNF) and interferon-gamma (IFN) modulate immune responses, as TNF is postulated as a first messenger for priming immune cells and IFN as the second messenger for activation. Nitric oxide (NO) is also an important mediator of immune function, as NO produced by immune cells in response to cytokines such as TNF and IFN may be a cytotoxic end-product effector of immune activation. To examine TNF and IFN modulation of NO production and effects upon allograft survival, we studied the in vitro effect of TNF, IFN, and lipopolysaccharide (LPS, as a nonspecific immune stimulator and TNF promoter) singly or together on NO production in unstimulated rat splenocytes or in response to allogeneic stimulation in MHC mismatch (Brown-Norway, BN, vs Lewis, LEW) mixed lymphocyte reactions. Nitrite as a stable reaction product of NO was determined by a colorimetric method based on the Griess reaction. Interestingly, unstimulated cells had little NO production in response to TNF or IFN; however, following nonspecific (LPS) or allogeneic stimulation there was a significant upregulation of NO production that was synergistically enhanced by the presence of both TNF and IFN. Significantly, anti-TNF antibody inhibited NO production up to 60% in all groups. In vivo studies used a cardiac heterotopic allotransplant model, again BN to LEW. Control recipients received no immunotherapy. Experimental recipients received IFN alone, anti-IFN antibody, anti-TNF antibody, or anti-TNF and anti-IFN antibody. Results from these allograft experiments showed no influence on survival by IFN alone or anti-IFN antibody alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Characterization of a new human glioblastoma cell line that expresses mutant p53 and lacks activation of the PDGF pathway.

We have established and characterized a new glioblastoma cell line, termed GT9, from a biopsy sample of a female adult patient with glioblastoma multiforme. The line has now undergone over 60 passages and has been successfully cultured after cryopreservation. Immunofluorescence analyses with a panel of monoclonal antibodies were positive for glial fibrillary acidic protein and vimentin, and negative for neurofilament, galactocerebroside, and fibronectin, a pattern typical of glial cells. Based on a tetraploid, the composite karyotype of GT9 cells included the loss of chromosome 10, gain of chromosome 7, and the presence of double minute chromosomes, three of the most common karyotypic abnormalities in glioblastoma. Sequence analysis of p53 cDNA revealed a homozygous double mutation at codon 249 (commonly mutated in aflatoxin-associated hepatocellular carcinoma) and codon 250. Moreover, there was a complete absence of wild-type p53. However, unlike the majority of human glioblastomas previously described, the expression of platelet-derived growth factor-B (PDGF-B), a potent mitogenic autocrine factor, was low in GT9 cells. The expression and phosphorylation of c-Jun and Jun-B, downstream mediators of the PDGF pathway, were also low. Thus, deregulation of the PDGF pathway does not appear to be involved in the pathogenesis of the GT9 glioblastoma. Conversely, Jun-D, a negative regulator of cell growth, was also low. In addition, Phosphorylated Egr-1, a recently reported suppressor of PDGF-B/v-sis-transformed cells, was also low, suggesting that the lack of activation of the PDGF pathway was not due to these suppressive mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Tb3+ binding to human erythrocyte spectrin resulting in conformation change and aggregation.

The Tb3+ binding to spectrin tetramer (SPT) was studied by Tb3+ fluorescence titration and CD spectra. The results indicated that the total high-affinity Tb3+ binding sites are n1 = 330, with average Kd = 3.6 x 10(-6) M. Among them, ca. 90 sites are of higher affinity and are probably more specific to Tb3+ than the remaining sites. There are 520 low affinity Tb3+ binding sites with average Kd = 1.5 x 10(-5) M. Fluorescence and CD spectra revealed that the alpha-helix content of SPT decreased with Tb3+ binding to specific sites and further binding did not result in conformation change. Tb3+ binding to SPT and the subsequent reactions were studied by employing stopped-flow fluorescence and light scattering methods. The studies demonstrate that this is a multistep reaction assembly: high-affinity terbium binding-conformation change-aggregation-low-affinity terbium binding--the second conformation change. The critical Tb3+ concentration-induced spectrin dimer (SPD) aggregation was determined with a light scattering method.

Binding Sites↗

Increasing mean skin temperature linearly reduces the core-temperature thresholds for vasoconstriction and shivering in humans.

BACKGROUND: The contribution of mean skin temperature to the thresholds for sweating and active precapillary vasodilation has been evaluated in numerous human studies. In contrast, the contribution of skin temperature to the control of cold responses such as arteriovenous shunt vasoconstriction and shivering is less well established. Accordingly, the authors tested the hypothesis that mean skin and core temperatures are linearly related at the vasoconstriction and shivering thresholds in men. Because the relation between skin and core temperatures might vary by gender, the cutaneous contribution to thermoregulatory control also was determined in women. METHODS: In the first portion of the study, six men participated on 5 randomly ordered days, during which mean skin temperatures were maintained near 31, 34, 35, 36, and 37 degrees C. Core hypothermia was induced by central venous infusion of cold lactated Ringer's solution sufficient to induce peripheral vasoconstriction and shivering. The core-temperature thresholds were then plotted against skin temperature and a linear regression fit to the values. The relative skin and core contributions to the control of each response were calculated from the slopes of the regression equations. In the second portion of the study, six women participated on three randomly ordered days, during which mean skin temperatures were maintained near 31, 35, and 37 degrees C. At each designated skin temperature, core hypothermia sufficient to induce peripheral vasoconstriction and/or shivering was again induced by central venous infusion of cold lactated Ringer's solution. The cutaneous contributions to control of each response were then calculated from the skin- and core-temperature pairs at the vasoconstriction and shivering thresholds. RESULTS: There was a linear relation between mean skin and core temperatures at the response thresholds in the men: r = 0.90 +/- 0.06 for vasoconstriction and r = 0.94 +/- 0.07 for shivering. Skin temperature contributed 20 +/- 6% to vasoconstriction and 19 +/- 8% to shivering. Skin temperature in the women contributed to 18 +/- 4% to vasoconstriction and 18 +/- 7% to shivering, values not differing significantly from those in men. There was no apparent correlation between the cutaneous contributions to vasoconstriction and shivering in individual volunteers. CONCLUSIONS: These data indicate that skin and core temperatures contribute linearly to the control of vasoconstriction and shivering in men and that the cutaneous contributions average approximately 20% in both men and women. The same coefficients thus can be used to compensate for experimental skin temperature manipulations in men and women. However, the cutaneous contributions to each response vary among volunteers; furthermore, the contributions to the two responses vary within volunteers.

Adult↗

Potassium's cardiovascular protective mechanisms.

High rates of potassium intake are associated with protection from cardiovascular diseases in populations consuming primitive diets and in vegetarians living in industrialized cultures. In studies in humans and in animals, a strong inverse association between potassium intake and hypertension and stroke has been described. However, acceptance of the putative protective effect has been limited by inadequate understanding of 1) long-term potassium regulation, and 2) mechanisms by which small changes in plasma potassium concentration may affect development of cardiovascular diseases. In this review, we present results from analyses of long-term potassium regulation that indicated 1) changes in potassium intake may result in potassium concentrations from 3.1 to 4.6 mmol/l, and 2) when the initial rate is below normal, potassium concentration is very sensitive to changes in potassium intake rate. In addition, we present results that provide bases for possible mechanisms by which potassium may protect against cardiovascular diseases: 1) increases in potassium inhibit free radical formation from vascular endothelial cells and macrophages; 2) elevation of potassium inhibits proliferation of vascular smooth muscle cells; 3) platelet aggregation and arterial thrombosis are inhibited by elevation of potassium; and 4) renal vascular resistance is reduced and glomerular filtration rate is increased by elevation of plasma potassium. We propose that elevation of dietary potassium intake increases plasma potassium concentration, thereby inhibiting free radical formation, smooth muscle proliferation, and thrombus formation. As a result, the rate of atherosclerotic lesion formation and thrombosis will be diminished. In addition, we propose the increase in glomerular filtration rate will cause a shift in the relationship between arterial pressure and sodium excretion that will lead to a reduction in arterial blood pressure. By these actions, high levels of dietary intake of potassium could provide the observed protection against the cardiovascular diseases that have plagued humankind since we began eating a modern high-sodium, low-potassium diet.

Animals↗

Survey of the conjugated linoleic acid contents of dairy products.

The objective of this research was to determine the content of conjugated linoleic acid, an anticarcinogen, in dairy products. Fifteen cheeses, three fermented dairy products (other than cheeses), and four fluid milk products (two brands for each product) were included in the survey. Total lipids, fatty acids, protein, moisture, and titratable acidity were also measured to determine the relationship between the content of these constituents and conjugated linoleic acid content. The conjugated linoleic acid content of cheeses ranged from 3.59 to 7.96 mg/g of lipid. Blue, Brie, Edam, and Swiss cheeses had significantly higher conjugated linoleic acid content than the other cheeses. Sharp Cheddar cheeses tended to have higher conjugated linoleic acid content than the medium Cheddar cheeses, but the increase was not significant. The conjugated linoleic acid content of the other fermented dairy products ranged from 3.82 to 4.66 mg/g of lipid, and cultured buttermilk had the highest content. The conjugated linoleic acid contents of four fluid milks ranged from 3.38 to 6.39 mg/g of lipid and were not significantly different from one another. Multiple linear regressions of conjugated linoleic acid content and the total fatty acid content indicated a relationship between conjugated linoleic acid content and the content of precursors and intermediates of conjugated linoleic acid formation, including linoleic and oleic acids.

Animals↗

[Diagnosis and misdiagnosis of fracture of the femoral head].

164 cases of traumatic posterior dislocation of the hip, of which 26 were associated with fractures of the femoral head, about 15.9% incidence, were treated during the year from March 1982 to March 1993. According to the pipkin classification of fractures of the femoral head, 10 cases were type 1, 6 tupe 2, 2 type 3, and 8 type 4. Of the 26 cases, 24 received emergent radiography, with 22 diagnosed and 2 misdiagnosed. The other 2 cases were found prompt auto-reduction of dislocation of the femoral head, without emergent radiography. The 4 misdiagnosed cases, because of continued pain or redislocation, came back later for radiography and then were correctly diagnosed. Besides the routine anteroposterior radiograph of the hip, pelvic oblique radiography angled 45 degrees or 60 degrees, and frog-leg anteroposterior hip radiography were needed. The CT-directed pelvic oblique radiograph was found to be the most accurate determinant of the extent of fracture displacement and the presence of intrasarticular loose fragments. Among the 19 cases operated on, 16 showed excellent-good rate (50%), and among the 7 non-operated cases, of 6 showed excellent-good rate (33%). After follow up.

Adolescent↗

[Biomechanics of bone in experimental diabetic rats].

The biomechanics of bone in diabetics and its response to insulin treatment was not clear. We investigated the impact of alloxan-induced diabetes and insulin treatment on the biomechanical characteristics of bones. Sprague-Dawley rats were divided into three groups: normal control (NC), diabetics (DM), and diabetics treated with insulin (DI). After 3 months the rats were killed. The load at bending test of the femurs was significantly decreased in DM compared to NC and DI. There was no statistical difference between DI and NC. Structurally, DM was significantly lower than NC and DI in the stress at the proportional limit and the maximum load of vertebrae. In material properties, marked deteriorations in the vertebrae were observed in DM and DI. The plasticity of the vertebrae observed in NC disappeared in DM, in which fragility was obvious. DI was not different from DM. We found that the structure and the material property of the bones deteriorate significantly in diabetes induced by alloxan. Insulin treatment inhibits most of biomechanical changes in bone induced by experimental diabetes, but not all of them. The data suggests that the relations between insulin and the material properties of diabetic bones remain to be studied.

Animals↗

[Effect of glucocorticoid receptor blockade on pulmonary and renal vascular permeability in scalded rats].

With glucocorticoid receptor (GR) blockade by RU38486, a competitive antagonist of GR, the change in contents of FITC labeled albumin (FITC-albumin) in pulmonary and renal tissue in scalded rats have been measured to study the changes in vascular permeability. The result showed that the contents of FITC-albumin in pulmonary and renal tissue in the scalded rats were markedly higher than those of the controls (lung: P < 0.05, kidney: P < 0.001). When the scalded rats were given GR blockade, the contents of FITC-albumin in pulmonary and renal tissue were significantly higher than those of rats with scald only (P < 0.05). The results indicated: (1) the pulmonary and renal vascular permeability in scalded rats was markedly enhanced; (2) GR blockade might aggravate the increase in vascular permeability caused by scald, so that the protective effect of glucocorticoid (GC) on vascular permeability seemed to be reversed.

Animals↗

Extensive wound excision in shock stage in patients with major burns.

To stop excessive plasma loss, alleviate noxious effects of devitalized tissues on the body and shorten the hospitalization time, we performed extensive escharectomy during the shock period in extensively burned patients. Group A consisted of 21 patients aged 9-45 years (26.1 +/- 7.9 years), with a mean total burn area of 63.2% +/- 18.1% TBSA, and full-thickness injury involving 35.9% +/- 19.6% TBSA. The first escharectomy was done at 24.1 +/- 13.9 hours postburn, and excision area averaged 32.3% +/- 6.7% TBSA (24%-46%). In 15 of them, Swan-Ganz catheter was introduced to monitor the hemodynamic changes. It was found that RAP, PAP, PAWP, ABP, HR, CO and CI were all stable during and after the operation. Group B consisted of 29 patients aged 11-50 years (30.4 +/- 11.7 years), in whom escharectomy was begun 4-5 days postburn. The mean healing time of the patients in group A was 33.1 days, shorter than that of group B patients (40.1 days). The duration of hemoconcentration was shorter in group A. The amount of blood transfusion was almost 700 ml less in group A during the first two weeks. Less antibiotics were used with fewer visceral complications in group A. We believe that escharectomy during the burn shock stage is feasible.

Adolescent↗

[Baseline hypertriglyceridemia, a risk factor for non-insulin dependent diabetes mellitus: a 6-year follow-up study of 432 nondiabetics].

The relationship between baseline fasting plasma triglycerides level (FTG) and the incidence of non-insulin-dependent diabetes mellitus (NIDDM) within 6 years were investigated in 432 Chinese nondiabetics. They were identified by oral glucose tolerance test (OGTT, oral 75 g glucose) in Daqing diabetes survey in 1986. 220 subjects were men and 212 women. Among them 226 had normal glucose tolerance and 206 impaired glucose tolerance. The measurement of fasting plasma lipids and glucose were performed at the baseline examination and after 6-year follow-up. Six-year incidence of NIDDM in the highest triglycerides tertile group (top tertile Q3, mean = 2.5 mmol/L) was 2.3 times (38.6% vs 16.6%, P < 0.01) as compared with that of the lowest triglycerides tertile group (first tertile Q1, mean = 0.7 mmol/L). The difference of 2-hour blood glucose level in OGTT (OGTT BG2h level) between Q1 and Q3 was 2.4 mmol/L (mean = 7.6-10.0 mmol/L) after 6 years. Multivariate general linear regression analysis demonstrated that the FTG level was positively associated with the OGTT BG2h level after 6 years (P = 0.0335) after controlling the age, sex, fasting blood glucose (FBG) and body mass index (BMI). Therefore this result indicates that FTG level is an independent risk factor for the development of NIDDM in this population.

Adult↗

[Gastric cancer with P53 overexpression and nm23 low-expression has high potential for lymph node metastasis].

By using SP immunohistochemical methods, the correlation of the expression of P53 and nm23 with the biologic behavior and lymph node metastasis in gastric carcinomas was studied. Abnormalities of P53 expression were found in 49% of the 88 primary gastric carcinomas. A significant correlation was found between P53 overexpression and the depth of invasion and the proliferative activities (Pearson Contingency Coefficient P = 0.32 and 0.35, P < 0.05, respectively). The metastatic rate of tumours stained positively for P53 (93%) were higher than in those with negative P53 staining (60%, P < 0.05). Meanwhile, a significant correlation of low expression of nm23 with the depth of cancer invasion was found (Pearson Contingency Coefficient P = 0.28, P < 0.05). nm23 low-expressive tumours were associated with a higher incidence of metastasis to lymph nodes (93%) than were nm23-normal expressive (49%, P < 0.05). The contributions of P53 overexpression and nm23 low-expression to the lymph nodal metastasis were the independent joint action. It is suggested that P53 overexpression and nm23 low-expression might play significant role in lymph node metastasis and invasion and proliferation in the primary gastric carcinomas.

Adenocarcinoma↗

Transgenic mice carrying the erythropoietin gene promoter linked to lacZ express the reporter in proximal convoluted tubule cells after hypoxia.

Results on the localization of erythropoietin (Epo) synthesis in renal cells have been contradictory, implicating either interstitial or tubular cells. We fused the lacZ gene to a 7-kb DNA fragment of the mouse Epo gene encompassing a portion of the first intron, the first exon, and a 6-kb sequence of the 5'-flanking region. Transgenic mice carrying this construct show a low level of specific expression of the lacZ gene in proximal convoluted tubule (PCT) cells. Without hypoxia, no significant expression was detected in the liver. Hypoxia induced a large degree of lacZ expression, mainly in kidney PCT cells and to a lesser degree in liver. However, anemia induced lacZ expression in both kidney and liver. These findings indicate that, under these conditions, Epo is expressed in tubular cells, specifically PCT cells.

Anemia↗

Decay-accelerating factor (CD55), a glycosylphosphatidylinositol-anchored complement regulatory protein, is a receptor for several echoviruses.

Echoviruses are human pathogens belonging to the picornavirus family. Decay-accelerating factor (DAF) is a glycosylphosphatidylinositol (GPI)-anchored surface protein that protects cells from lysis by autologous complement. Anti-DAF monoclonal antibodies prevented echovirus 7 attachment to susceptible cells and protected cells from infection. HeLa cells specifically lost the capacity to bind echovirus 7 when treated with phosphatidylinositol-specific phospholipase C, an enzyme that releases GPI-anchored proteins from the cell surface, indicating that the virus receptor, like DAF, is a GPI-anchored protein. Although Chinese hamster ovary cells do not bind echovirus 7, transfectants expressing human DAF bound virus efficiently, and binding was prevented by pretreatment with an anti-DAF monoclonal antibody. Anti-DAF antibodies prevented infection by at least six echovirus serotypes. These results indicate that DAF is the receptor mediating attachment and infection by several echoviruses.

Animals↗

Maternal anti-placental reactivity in natural, immunologically-mediated fetal resorptions.

Observations on maternal recognition of the fetus and the demonstration of the effects of cytokines on reproductive events led to the "immunotrophism" model, which suggests that maternal immune recognition of fetally-derived Ags results in the release of cytokines that promote the growth of the placenta; any disturbance in this balance of cytokines could result in deleterious consequences for the placenta and, in turn, the fetus. We have focused our attention on the murine CBA/J x DBA/2 model of spontaneous abortions and compared them with normal CBA x BALB/c pregnancies. Our results indicate that the extent of stimulation of maternal strain lymphocytes in response to stimulator placental cells in mixed lymphocyte-placenta reactions (MLPR) was much higher in the normal mating combination compared with the abortion-prone mating combination. Cytokine analysis of the supernatants from MLPR indicates that there is significantly higher production of TNF-alpha, IFN-gamma, and IL-2 in supernatants from the abortion-prone combination than in supernatants from the normal combination. Furthermore, MLPR-stimulated cells induce resorptions in normal pregnant mice; maternal strain lymphocytes stimulated by placentas from the abortion-prone combination induce high rates of fetal resorptions, but lymphocytes stimulated with placentas from the normal combination do not. Together, these results suggest that immunologically mediated fetal resorptions probably result from improper or inappropriate maternal responses to placental Ags. Our observations also suggest that such effects are probably mediated by cytokines.

Animals↗

Specific region of the c-myc promoter is responsive to electric and magnetic fields.

The level of c-myc transcripts is increased in cells exposed to extremely low frequency (elf) electromagnetic (EM) fields at 60 Hz. The aim of the present experiments was to determine if regulatory regions upstream of the c-myc gene modulate the response to EM fields. DNA upstream of P1 of both mouse and human c-myc genes was transfected into cells as CAT constructs. The presence of DNA 5' to the human or mouse myc genes results in increased expression of CAT following 20 min exposures of cells to 60 Hz elf EM fields. Specific portions of the human upstream DNA were deleted and introduced into cells. The region responsive to EM fields is located between -353 and -1,257 relative to the P1 promoter.

Animals↗