Interventional techniques for treatment of disease in the brachiocephalic arteries (supra-aortic trunks)
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Biomedical subjects
Publications and source records attributed to J A Martin.
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Throughout life chondrocytes maintain the articular cartilage matrix by replacing degraded macromolecules and respond to focal cartilage injury or degeneration by increasing local synthesis activity. These observations suggest that mechanisms exist within articular cartilage that stimulate chondrocyte anabolic activity in response to matrix degradation or damage. An important cartilage anabolic factor, insulin-like growth factor I (IGF-I), appears to have a role in stimulating chondrocyte anabolic activity. Although IGF-I is ubiquitous, its bioavailability is controlled by a class of secreted proteins, IGF binding proteins (IGFPBs). Of the six known IGFPBs, IGFBP-3 is the most abundant in human articular cartilage. We recently found that with increasing age, articular chondrocytes increase their expression of IGFBP-3. This observation led us to investigate the potential role of IGFBP-3 in chondrocyte-matrix interactions. Using immunofluorescent staining and confocal microscopy we found that IGFBP-3 accumulates with increasing age in the chondrocyte territorial matrix where it co-localizes with fibronectin, but not with tenascin-C or type VI collagen. Using purified proteins we demonstrated that IGFBP-3 binds to fibronectin in a dose dependent manner, but not to tenascin-C. In vitro studies showed that IGFBP-3 alone inhibited chondrocyte synthetic activity while intact fibronectin alone significantly stimulated activity. When fibronectin and IGFBP-3 were combined we found that the inhibitory activity of low concentrations of IGFPB-3 was enhanced. These observations indicate that in mature articular cartilage IGF-I is stored in the chondrocyte territorial matrix through binding to a complex of IGFPB-3 and intact fibronectin. Storage of IGF-I of the territorial matrix may help maintain a relatively constant level of available IGF-I and the local increase in matrix synthesis following matrix damage may result from release of IGF-I. This mechanism may have an important role in maintaining and repairing articular cartilage and failure of this mechanism may lead to progressive articular cartilage degeneration.
Articular chondrocytes maintain cartilage throughout life by replacing lost or damaged matrix with freshly synthesized material. Synthesis activity is regulated, rapidly increasing to well above basal levels in response to cartilage injury. Such responses suggest that synthesis activity is linked to the rate of matrix loss by endogenous "damage control" mechanisms. As a major stimulator of matrix synthesis in cartilage, insulin-like growth factor I (IGF-I) is likely to play a role in such mechanisms. Although IGF-I is nearly ubiquitous, its bioavailability in cartilage is controlled by IGF-I binding proteins (IGFBPs) secreted by chondrocytes. IGFBPs are part of a complex system, termed the IGF-I axis, that tightly regulates IGF-I activities. For the most part, IGFBPs block IGF-I activity by sequestering IGF-I from its cell surface receptor. We recently found that the expression of one binding protein, IGFBP-3, increases with chondrocyte age, paralleling an age-related decline in synthesis activity. In addition, IGFBP-3 is overexpressed in osteoarthritic cartilage, leading to metabolic disturbances that contribute to cartilage degeneration. These observations indicate that IGFBP-3 plays a crucial role in regulating matrix synthesis in cartilage, and suggest that cartilage damage control mechanisms may fail due to age-related changes in IGFBP-3 expression or distribution. Our investigation of this hypothesis began with immunolocalization studies to determine the tissue distribution of IGFBP-3 in human cartilage. We found that IGFBP-3 accumulated around chondrocytes in the pericellular/territorial matrix, where it co-localized with fibronectin, but not with the other matrix proteins tenascin-C and type VI collagen. This result suggested that the IGFBP-3 distribution is determined by binding to fibronectin. Binding studies using purified proteins demonstrated that IGFBP-3 does in fact bind to fibronectin, but not to tenascin-C or type VI collagen. Finally, we investigated the metabolic effects of fibronectin and IGFBP-3 in a chondrocyte culture system. These experiments showed that fibronectin enhanced the inhibitory effect that low concentrations of IGFBP-3 had on matrix synthesis. Taken together, these observations confirm that IGFBP-3-fibronectin interactions affect the IGF-I axis, and they indicate that IGF-I is stored in the chondrocyte territorial matrix through binding to a complex of IGFBP-3 and intact fibronectin. This arrangement may play an important role in cartilage damage control mechanisms. The local increase in matrix synthesis following injury could result from damage-induced IGF-I release from such pools. An age-related failure to organize this system may contribute to degenerative disease.
OBJECTIVES: This report presents preliminary data for 1998 on births and deaths in the United States. U.S. data on births are shown by age, race, and Hispanic origin of mother. Natality data on marital status, prenatal care, cesarean delivery, and low birthweight are also presented. Mortality data presented include life expectancy, leading causes of death, and infant mortality. METHODS: Data in this report are based on more than a 99-percent sample of births and on more than an 85-percent sample of deaths in the United States for 1998. The records are weighted to independent control counts of births, infant deaths, and deaths 1 year and over received in State vital statistics offices in 1998. Comparisons are made with 1997 final data. RESULTS: The birth rate for teenagers continued to decline, dropping another 2 percent for 1997-98. The rate for young teens aged 15-17 years fell 5 percent, and the rate for teens aged 18-19 years declined 2 percent. Since 1991 rates have fallen 21 percent for teens aged 15-17 years and 13 percent for teens aged 18-19 years. Birth rates for women aged 20-29 years rose slightly. Among women in their thirties, birth rates rose 3 to 4 percent to the highest levels observed in three decades. The birth rate for women aged 40-44 years was the highest level reported since 1970. The birth rate for unmarried women was 44.3 per 1,000, 1 percent higher than 1997, but below the peak level reported for 1994 (46.9). The rate of prenatal care utilization continued to improve. The total cesarean rate increased to 21.2 percent. The low birthweight rate rose from 7.5 to 7.6 percent. In 1998 the age-adjusted death rate reached a record low, 2 percent below the rate for 1997. Human immunodeficiency virus infection (HIV infection) moved off the list of the 15 leading causes of death for the first time since 1987. Declines in age-adjusted rates occurred for Homicide and legal intervention (homicide) (14 percent) and Atherosclerosis (10 percent), while rates for Septicemia and Pneumonia and influenza increased 5 percent. Mortality also decreased for drug-induced deaths, deaths from injury by firearms, and alcohol-induced deaths. The infant mortality rate was unchanged. Life expectancy reached a record high of 76.7 in 1998.
This report presents data from U.S. birth certificates on the numbers and rates of twin and triplet and other higher order multiple births for 1980-97. Over the study period, the number of twin births rose 52 percent (from 68,339 to 104,137) and triplet and other higher order multiple births (heretofore referred to as "triplet/+") climbed 404 percent (from 1,337 to 6,737 births). Comparable but less pronounced rises were observed in twin and triplet/+ birth rates. Growth in twin and triplet/+ birth rates was most marked among women aged 30 years and over. Between 1980-82 and 1995-97, the twin rate rose 63 percent for women aged 40-44 years, and soared nearly 1,000 percent for women 45-49 years. (As one result, there were more twins born to women 45-49 years of age in 1997, than during the entire decade of the 1980's.) The triplet/+ birth rate rose nearly 400 percent for women in their thirties and exploded by more than 1,000 percent for women in their forties. The extraordinary rise in multiple births resulted in a shift in age-specific patterns, and the highest twin and triplet/+ birth rates now are for women 45-49 years of age. Historical differences in twinning rates between non-Hispanic white and black mothers have been largely eliminated (28.8 per 1,000 non-Hispanic white compared with 30.0 for black women). Non-Hispanic white women were more than twice as likely as non-Hispanic black or Hispanic women to have a triplet/+ birth. Rates of low birthweight, very low birthweight, and infant mortality were 4 to 33 times higher for twins and triplet/+ compared with singleton births. The risk for these adverse outcomes was lowest for twins and triplet/+ born to women 35-44 years of age. Twin birth rates for Massachusetts and Connecticut were at least 25 percent higher than the U.S. rate; triplet/+ rates for Nebraska and New Jersey were twice the national level.
OBJECTIVES: This report presents preliminary data on births and deaths in the United States from the National Center for Health Statistics (NCHS) for the 12 months ending June 1998. U.S. data on births are shown by age, race, and Hispanic origin of mother. Natality data on marital status, prenatal care, cesarean delivery, and low birthweight are also presented. Mortality data presented include leading causes of death and infant mortality. METHODS: Data in this report are based on more than a 99-percent sample of births and on more than an 89-percent sample of deaths in the United States for the 12 months ending June 1998. The records are weighted to independent control counts of births, infant deaths, and deaths 1 year and over received in State vital statistics offices from July 1997 to June 1998. Unless otherwise indicated, comparisons are made with final data for the 12-month period ending June 1997. RESULTS: For the period July 1997-June 1998, the birth rate for teenagers dropped 4 percent to 51.5 births per 1,000 women aged 15-19 years, the lowest level since 1987. Birth rates for teenagers have been declining since 1991. Birth rates for women aged 20-29 years changed very little, whereas rates for women in their thirties and forties rose 2 to 4 percent. The birth rate for unmarried women declined slightly, but the number of births to unmarried women was up about 1 percent because of an increase in the number of unmarried women. The rate of prenatal care utilization continued to improve. The percent of births delivered by cesarean section rose from 20.7 percent to 20.9 percent as the result of a slight increase in the primary cesarean rate and a substantial decline in the rate of vaginal births after previous cesarean (VBAC). The overall low birthweight rate was unchanged at 7.5 percent. Age-adjusted death rates reached a record low, 2 percent below the rate for the previous 12-month period. The largest declines in estimated age-adjusted death rates among the leading causes of death were for Human immunodeficiency virus (HIV) infection (37 percent) and homicide (9 percent). Smaller declines were noted for most of the other leading causes of death, but no increases occurred. Mortality also decreased for firearm injuries and alcohol-induced deaths. The infant mortality rates for all races and white and black infants were about the same as the corresponding rates for the previous 12-month period.
OBJECTIVES: This report presents 1997 data on U.S. births according to a wide variety of characteristics. Data are presented for maternal demographic characteristics including age, live-birth order, race, Hispanic origin, marital status, and educational attainment; maternal lifestyle and health characteristics (medical risk factors, weight gain, and tobacco and alcohol use); medical care utilization by pregnant women (prenatal care, obstetric procedures, complications of labor and/or delivery, attendant at birth, and method of delivery); and infant health characteristics (period of gestation, birthweight, Apgar score, abnormal conditions, congenital anomalies, and multiple births). Also presented are birth and fertility rates by age, live-birth order, race, Hispanic origin, and marital status. Selected data by mother's State of residence are shown including teenage birth rates and total fertility rates, as well as data on month and day of birth, sex ratio, and age of father. Trends in fertility patterns and maternal and infant characteristics are described and interpreted. METHODS: Descriptive tabulations of data reported on the birth certificates of the 3.9 million births that occurred in 1997 are presented. RESULTS: Birth and fertility rates declined very slightly in 1997. Birth rates for teenagers fell 3 to 5 percent. Rates for women in their twenties changed very little, whereas rates for women in their thirties rose 2 percent. The number of births and the birth rate for unmarried women each declined slightly in 1997 while the percent of births that were to unmarried women was unchanged. Smoking by pregnant women overall dropped again in 1997, but continued to increase among teenagers. Improvements in prenatal care utilization continued. The cesarean delivery rate increased slightly after declining for 7 consecutive years. The proportion of multiple birth continued to rise; higher order multiple births (e.g., triplets, quadruplets) rose by 14 percent in 1997, following a 20 percent rise from 1995 to 1996. Key measures of birth outcome--the percents of low birthweight and preterm births--increased, with particularly large increases in the preterm rate. These changes are in large part the result of increases in multiple births.
BACKGROUND: Endoscopically placed biliary stents have become routine therapy for bile duct obstruction and bile leaks. Controversy exists regarding the use of biliary sphincterotomy to facilitate placement of 10F plastic stents. METHODS: We retrospectively studied the effect of sphincterotomy on acute and chronic complications of 10F stent therapy. Data for acute complications, 30-day mortality and stent migration were obtained for 130 patients undergoing placement of a single 10F plastic biliary stent. For 109 patients in whom prolonged stent therapy was undertaken, the occurrence of and time to stent dysfunction were also analyzed. Sphincterotomy was performed in 48 cases (36.9%) based on physician preference. RESULTS: There were no failures in stent placement. The incidence of acute complications was higher in patients undergoing sphincterotomy (8.3% vs. 1.2%, p = 0.04). Stent migration was more common in the no sphincterotomy group versus the sphincterotomy group (8.5% vs. 0, p = 0.03). CONCLUSIONS: Sphincterotomy is not necessary for placement of 10F plastic stents and increases acute procedural morbidity. Interestingly, a higher incidence of stent migration was seen in patients who did not undergo biliary sphincterotomy.
Jaundice in hepatocellular carcinoma (HCC) can be due to biliary obstruction. Endoscopic retrograde cholangiopancreatography (ERCP) can be both diagnostic and therapeutic. Biliary stenting can relieve jaundice and allow further chemotherapy, but at additional expense and potential morbidity. We sought to determine whether CT scan or ultrasound (US) could identify which patients with HCC and jaundice would benefit from endoscopic stenting. We retrospectively analyzed 26 patients with HCC and jaundice who underwent ERCP after CT or US. We compared biliary dilation on CT or US with the dominant biliary stricture seen on ERCP, and with response to biliary stenting. Eleven of 26 patients had dominant biliary stricture on ERCP; 11 underwent stenting. Six of 11 (55%) stented patients had a significant decline in bilirubin; three became eligible for further chemotherapy. All six responders to stenting had biliary dilation on prior CT or US. Procedure-related complications occurred in 1/11 (9%) who underwent stent placement. In conclusion, in selected patients, stenting can safely relieve jaundice and allow subsequent chemotherapy. CT or US accurately predicted lesions that responded to stenting. ERCP and stenting provided no benefit in the absence of biliary dilation on CT or US.
Most vital statistics indicators of the health of Americans were stable or showed modest improvements between 1997 and 1998. The preliminary birth rate in 1998 was 14.6 births per 1000 population, up slightly from the record low reported for 1997 (14.5). The fertility rate, births per 1000 women aged 15 to 44 years, increased 1% to 65.6 in 1998, compared with 65.0 in 1997. The 1998 increases, although modest, were the first since 1990, halting the steady decline in the number of births and birth and fertility rates in the 1990s. Fertility rates for total white, non-Hispanic white, and Native American women each increased from 1% to 2% in 1998. The fertility rate for black women declined 19% from 1990 to 1996, but has changed little since 1996. The rate for Hispanic women, which dropped 2%, was lower than in any year for which national data have been available. Birth rates for women 30 years or older continued to increase. The proportion of births to unmarried women remained about the same at one third. The birth rate for teen mothers declined again for the seventh consecutive year, and the use of timely prenatal care (82.8%) improved for the ninth consecutive year, especially for black (73.3%) and Hispanic (74.3%) mothers. The number and rate of multiple births continued their dramatic rise; the number of triplet and higher-order multiple births jumped 16% between 1996 and 1997, accounting, in part, for the slight increase in the percentage of low birth weight (LBW) births. LBW continued to increase from 1997 to 1998 to 7.6%. The infant mortality rate (IMR) was unchanged from 1997 to 1998 (7.2 per 1000 live births). The ratio of the IMR among black infants to that for white infants (2.4) remained the same in 1998 as in 1997. Racial differences in infant mortality remain a major public health concern. In 1997, 65% of all infant deaths occurred to the 7.5% of infants born LBW. Among all of the states, Maine, Massachusetts, and New Hampshire had the lowest IMRs. State-by-state differences in IMR reflect racial composition, the percentage LBW, and birth weight-specific neonatal mortality rate for each state. The United States continues to rank poorly in international comparisons of infant mortality. Expectation of life at birth increased slightly to 76.7 years for all gender and race groups combined. Death rates in the United States continue to decline, including a drop in mortality from human immunodeficiency virus. The age-adjusted death rate for suicide declined 6% in 1998; homicide declined 14%. Death rates for children from all major causes declined again in 1998. A large proportion of childhood deaths, however, continue to occur as a result of preventable injuries.
OBJECTIVE: This study examines the impact of maternal nativity (birthplace) on the overall prevalence of diabetes during pregnancy and among 15 racial and ethnic groups in the U.S. RESEARCH DESIGN AND METHODS: Birth certificate data for all resident single live births in the U.S. from 1994 to 1996 were used to calculate reported diabetes prevalence during pregnancy and to assess the impact of maternal birthplace outside of the 50 states and Washington, DC, on the risk of diabetes before and after adjustment for differences in maternal age, other sociodemographic characteristics, and late or no initiation of prenatal care overall and for each racial and ethnic group. RESULTS: Mothers born outside of the U.S. are significantly more likely to have diabetes during pregnancy. The impact of maternal nativity on diabetes prevalence is largely explained by the older childbearing age of immigrant mothers. However, adjusted diabetes risk remains elevated for Asian-Indian, non-Hispanic black, Filipino, Puerto Rican, and Central and South American mothers who were born outside the U.S. Conversely, birthplace outside the U.S. significantly reduces diabetes risk for Japanese, Mexican, and Native American women. CONCLUSIONS: Identification, treatment, and follow-up of immigrant mothers with diabetes during pregnancy may require special attention to language and sociocultural barriers to effective care. Systematic surveillance of the prevalence and impact of diabetes during pregnancy for immigrant and nonimmigrant women, particularly in racial and ethnic minority groups, and more detailed studies on the impact of acculturation on diabetes may increase understanding of the epidemiology of diabetes during pregnancy in our increasingly diverse society.
OBJECTIVES: This report presents preliminary data on births and deaths in the United States from the National Center for Health Statistics (NCHS) for 1997. U.S. data on births are shown by age, race, and Hispanic origin of mother. National and State data on marital status, prenatal care, cesarean delivery, and low birthweight are also presented. Mortality data presented include life expectancy, leading causes of death, and infant mortality. METHODS: Data in this report are based on a 99 percent sample of births and more than an 85 percent sample of deaths in the United States in 1997. The records are weighted to independent control counts of births, infant deaths, and deaths 1 year and over received in State vital statistics offices in 1997. RESULTS: According to preliminary data for 1997, the birth rate for teenagers dropped to 52.9 births per 1,000 women aged 15-19 years, 3 percent lower compared with 1996. Birth rates for teenagers have been declining since 1991. Declines for younger teenagers (15-17 years) were greater than for older teenagers. Birth rates for women aged 25-44 years increased 1 to 2 percent; the rate for women aged 20-24 years rose very slightly. The number of births to unmarried women was essentially unchanged and the percent of all births to unmarried women remained at 32.4 percent; the birth rate for unmarried women declined 2 percent. The rate of prenatal care utilization continued to improve. The cesarean delivery rate increased slightly. The overall low birthweight rate increased to 7.5 percent. The largest declines in estimated age-adjusted death rates among the leading causes of death were for Human immunodeficiency virus (HIV) infection (47 percent) and homicide (12 percent). Mortality also decreased for firearm injuries, drug-induced deaths, and alcohol-induced deaths. The age-adjusted death rate increased for Pneumonia and influenza, Chronic obstructive pulmonary diseases, kidney disease, and Septicemia. The preliminary infant mortality rate for 1997 was 7.1 infant deaths per 1,000 live births, down from a rate of 7.3 for 1996. The infant mortality rate for black infants declined 7 percent to 13.7; the white rate was 6.0. Life expectancy reached a record high of 76.5 years in 1997.
OBJECTIVES: This report presents 1996 data on U.S. births according to a wide variety of characteristics. Data are presented for maternal demographic characteristics including age, live-birth order, race, Hispanic origin, marital status, and educational attainment; maternal lifestyle and health characteristics (medical risk factors, weight gain, tobacco and alcohol use); medical care utilization by pregnant women (prenatal care, obstetric procedures, complications of labor and/or delivery, attendant at birth, and method of delivery); and infant health characteristics (period of gestation, birthweight, Apgar score, abnormal conditions, congenital anomalies, and multiple births). Also presented are birth and fertility rates by age, live-birth order, race, Hispanic origin, and marital status. Selected data by mother's State of residence are shown including teenage birth rates and total fertility rates, as well as data on month and day of birth, sex ratio, and age of father. Trends in fertility patterns and maternal and infant characteristics are described and interpreted. METHODS: Descriptive tabulations of data reported on the birth certificates of the 3.9 million births that occurred in 1996 are presented. RESULTS: Birth and fertility rates declined very slightly in 1996. Birth rates for teenagers fell 3 to 8 percent. Rates for women in their twenties increased slightly in 1996, the first increase since 1990, while rates for women in their thirties rose 2 to 3 percent. The number and percent of births to unmarried women increased slightly in 1996 while the birth rate for unmarried women declined modestly. Smoking by pregnant women overall dropped again in 1996, but increased among teenagers. Improvements in prenatal care utilization continued. The cesarean delivery rate declined. The proportion of multiple births continued to rise; higher order multiple births (e.g., triplets, quadruplets) rose by 19 percent. Key measures of birth outcome--the percents of low birthweight and preterm births--increased slightly, in large part the result of increases in multiple births.
CONTEXT: Two measures traditionally used to examine adequacy of prenatal care indicate that prenatal care utilization remained unchanged through the 1980s and only began to rise slightly in the 1990s. In recent years, new measures have been developed that include a category for women who receive more than the recommended amount of care (intensive utilization). OBJECTIVE: To compare the older and newer indices in the monitoring of prenatal care trends in the United States from 1981 to 1995, for the overall population and for selected subpopulations. Second, to examine factors associated with receiving intensive utilization. DESIGN: Cross-sectional and trend analysis of national birth records. SETTING: The United States. SUBJECTS: All live births between 1981 and 1995 (N=54 million). MAIN OUTCOME MEASURES: Trends in prenatal care utilization, according to 4 indices (the older indices: the Institute of Medicine Index and the trimester that care began, and the newer indices: the R-GINDEX and the Adequacy of Prenatal Care Utilization Index). Multiple logistic regression was used to assess the risk of intensive prenatal care use in 1981 and 1995. RESULTS: The newer indices showed a steadily increasing trend toward more prenatal care use throughout the study period (R-GINDEX, intensive or adequate use, 32.7% in 1981 to 47.1 % in 1995; the Adequacy of Prenatal Care Utilization Index, intensive use, 18.4% in 1981 to 28.8% in 1995), especially for intensive utilization. Women having a multiple birth were much more likely to have had intensive utilization in 1995 compared with 1981 (R-GINDEX, 22.8% vs 8.5%). Teenagers were more likely to begin care later than adults, but similar proportions of teens and adults had intensive utilization. Intensive use among low-risk women also increased steadily each year. Factors associated with a greater likelihood of receiving intensive use in 1981 and 1995 were having a multiple birth, primiparity, being married, and maternal age of 35 years or older. CONCLUSIONS: The proportion of women who began care early and received at least the recommended number of visits increased between 1981 and 1995. This change was undetected by more traditional prenatal care indices. These increases have cost and practice implications and suggest a paradox since previous studies have shown that rates of preterm delivery and low birth weight did not improve during this time.
OBJECTIVES: This report presents trend data on births in the United States to women of Hispanic and non-Hispanic origin, from 1989 to 1995, for a wide variety of characteristics. Hispanic women data are presented where possible separately for Mexican, Puerto Rican, Cuban, Central and South American, and other Hispanic women while for non-Hispanic women data are shown for white and black women. Maternal demographic characteristics include age, marital status, live-birth order, educational attainment, and mother's place of birth. Health care utilization items include timing of prenatal care, cesarean delivery rate, place of birth and midwife attendance. Infant health characteristics include percents born preterm, low birthweight, very low birthweight, and percent born in multiple births. Trend data for the number of births by State are also presented. METHODS: Descriptive tabulations of births of Hispanic origin of the mother for births that occurred from 1989 through 1995 are presented. RESULTS: The number of births born to Hispanic women has risen every year from 1989 to 1995. In addition in 1989 Hispanic women had 14 percent of births in the United States and in 1995 they represented 18 percent. While Hispanic women as a group continue to have higher fertility rates than non-Hispanics, Mexican women in particular have dramatically higher rates. While increases in early prenatal care were observed for all women in the United States, increases were particularly substantial for Hispanic women. The cesarean section rate has been dropping in the United States; yet while rates for Cuban women have also been dropping, the rates are nearly 50 percent higher than those for any other population subgroup.
The effect of aging on indices of oxidative damage in rat mitochondria and the protective effect of the Ginkgo biloba extract EGb 761 was investigated. Mitochondrial DNA from brain and liver of old rats exhibited oxidative damage that is significantly higher than that from young rats. Mitochondrial glutathione is also more oxidized in old than in young rats. Peroxide formation in mitochondria from old animals was higher than in those from young ones. According to morphological parameters (size and complexity), there are two populations of mitochondria. One is composed of large, highly complex mitochondria, and the other population is smaller and less complex. Brain and liver from old animals had a higher proportion of the large, highly complex mitochondria than seen in organs from young animals. Treatment with the Ginkgo biloba extract EGb 761 partially prevented these morphological changes as well as the indices of oxidative damage observed in brain and liver mitochondria from old animals.
Hyaluronan is an integral component of proteoglycan-rich extracellular matrices such as hyaline cartilage. Hyaluronan is commonly found in embryonic tissue and is important in the formation of hydrated matrices that allow cellular expansion and migration. Cell surface hyaluronan-binding proteins such as CD44 are presumed to be important in the cellular interactions with hyaluronan in both of these processes. The primary aim of this study was to document the spatial and temporal expressions of CD44 isoforms during the development and growth of the diarthrodial joints of rat limbs. With use of in situ hybridization and immunohistochemistry, the CD44s isoform is selectively identified as localized to a single cell layer on opposing sides of the joint at the first appearance of joint cavitation (on the 18th day of gestation). After joint formation in the neonate, the expression of the CD44s isoform in the cells at the joint surface is lost. These findings suggest that the CD44s isoform has a role in the development of the diarthrodial joint, presumably through interaction with hyaluronan.
Fibronectin, a ubiquitous glycoprotein of the extracellular matrix, serves as a substrate for cell attachment. Binding to fibronectin through cell-surface receptors promotes a flattened cell shape, stimulates the phosphorylation of intracellular protein, and changes the pattern of gene expression. Although fibronectin is abundant in normal articular cartilage, its effects on chondrocytes are not well understood. Proteolytic fragments of fibronectin stimulate the catabolism of matrix in articular cartilage and may promote the degeneration of cartilage in osteoarthritis; however, intact fibronectin may regulate other aspects of matrix metabolism, including matrix synthesis. To determine whether intact fibronectin affects the synthetic activity of chondrocytes, as well as to determine the responses of chondrocytes to the anabolic growth factor insulin-like growth factor-I, we compared the incorporation of [35S] by articular chondrocytes of the rat cultured in the presence and absence of commercially prepared cellular fibronectin and 0, 10, or 100 ng/ml recombinant human insulin-like growth factor-I. Monolayer and alginate suspension cultures were compared to determine whether responses differed under conditions in which fibronectin promoted a flattened cell shape (monolayer culture) and under those in which cells maintained a spherical shape (alginate culture). In alginate cultures, fibronectin alone stimulated the incorporation of [35S]. Fibronectin with 10 ng/ml insulin-like growth factor-I had additive effects in alginate culture, producing the maximum incorporation of [35S]. In monolayer cultures, fibronectin did not stimulate incorporation and blocked stimulation by 100 ng/ml insulin-like growth factor-I. The cells from the monolayer culture were much less active synthetically (at all doses of the growth factor) than those cultured in alginate. Thus, fibronectin enhanced proteoglycan synthesis and the response to insulin-like growth factor-I in alginate but inhibited the response to the growth factor in monolayers. These observations suggest intact fibronectin may contribute to the maintenance or repair of the matrix of articular cartilage by stimulating proteoglycan synthesis.