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Biomedical subjects

M C Martin

Publications and source records attributed to M C Martin.

At least 19 recordsLinked to original sources

Observation of terahertz emission from a laser-plasma accelerated electron bunch crossing a plasma-vacuum boundary.

Coherent radiation in the 0.3-3 THz range has been generated from femtosecond electron bunches at a plasma-vacuum boundary via transition radiation. The bunches produced by a laser-plasma accelerator contained 1.5 nC of charge. The THz energy per pulse within a limited 30 mrad collection angle was 3-5 nJ and scaled quadratically with bunch charge, consistent with coherent emission. Modeling indicates that this broadband source produces about 0.3 microJ per pulse within a 100 mrad angle, and that increasing the transverse plasma size and electron beam energy could provide more than 100 microJ/pulse.

Journal Article↗

Cyclic AMP regulation of neutrophil apoptosis occurs via a novel protein kinase A-independent signaling pathway.

The second messenger molecule cyclic AMP dramatically modulates the apoptotic program in a wide variety of cells, accelerating apoptosis in some and delaying the rate of apoptosis in others. Human neutrophil apoptosis, a process that regulates the fate and numbers of these potentially histotoxic cells in inflammatory sites, is profoundly delayed by the cell-permeable analog of cyclic AMP, dibutyryl-cAMP. We have investigated the mechanisms underlying cyclic AMP-mediated delay of neutrophil apoptosis, and we show that cyclic AMP inhibits loss of mitochondrial potential occurring during constitutive neutrophil apoptosis. Furthermore, we demonstrate that cyclic AMP also suppresses caspase activation in these inflammatory cells. Despite increasing protein kinase A activity, this kinase is unlikely to mediate the effect of cyclic AMP on apoptosis because blockade of protein kinase A activation did not influence the survival effects of cyclic AMP. Further investigation of the signaling mechanism demonstrated that the delay of apoptosis is independent of phosphoinositide 3-kinase and MAPK activation. Our results suggest cyclic AMP delays neutrophil apoptosis via a novel, reversible, and transcriptionally independent mechanism. We show that proteasome activity in the neutrophil is vitally involved in this process, and we suggest that a balance of pro-apoptotic and anti-apoptotic proteins plays a key role in the powerful ability of cyclic AMP to delay neutrophil death.

Adenosine Monophosphate↗

Association of CD4+/CD56+/CD57+/CD8+(dim) large granular lymphocytic leukemia, splenic B-cell lymphoma with circulating villous lymphocytes, and idiopathic erythrocytosis.

In this paper we report a rare association of a splenic marginal zone B-cell lymphoma with villous lymphocytes and a T-cell large granular lymphocytic leukemia coexpressing CD4 and CD8 as well as CD56 and CD57 natural killer-associated markers in an asymptomatic patient investigated because of an occasional finding of erythrocytosis and leukocytosis in routine blood analysis. We also discuss the possible reasons for this particular association.

Aged↗

Visualizing rhizosphere chemistry of legumes with mid-infrared synchrotron radiation.

A bright synchrotron light source operated by the Lawrence Berkeley National Laboratory served as an external source for infrared (IR) microscopy of plant root microcosms. Mid-IR light from synchrotrons is 2-3 orders of magnitude brighter than conventional sources, providing contrast based on the chemical information in the reflected signal at a spatial resolution near the diffraction-limit of 3-10 microm. In an experiment using plant root microcosms fitted with zinc selenide IR-transmissive windows (50 mm x 20 mm x 1 mm), we describe chemical differences and similarities within the root zone of mung bean (Vigna radiata L.), grown with or without phosphorus, and revealed by reflectance spectromicroscopy. Comparative root and root-exudate profiles are described in sand/silt culture over the wavelength range of 2.5 to 16 pm (4.000 to 650 cm(-1) ) in the mid-IR. the spectral region most useful for the analytical identification of small organic molecules. Root epidermal tissue of plants grown with low phosphorus showed a greater lipid contribution and less lignin than nutrient-sufficient plants. In the zone 200 microm from the root axis, control plants were enriched with simple sugars and monomeric lignin precursors. In low-phosphorus plants, the rhizosphere possessed IR signatures from protein and sugars. Individual soil minerals could be easily discriminated from biological material. Synchrotron IR spectromicroscopy, therefore, complements existing root imaging techniques.

Fabaceae↗

Role of stress responses in human cell survival following exposure to ultraviolet C radiation.

PURPOSE: To investigate in human skin and other cells the role of tyrosine kinase and protein kinase-C (PKC) in eliciting cell-signalling responses to UV radiation (UVR) that affect the survival of irradiated cells. MATERIALS AND METHODS: The survival of HeLa S3 cells, NCTC 2544 human keratinocytes and A431 human epidermal carcinoma cells was measured following incubation with various tyrosine kinase or PKC inhibitors and exposure to UVC (254nm) radiation. In addition, Western blotting measured PKC isozyme expression in human keratinocytes following UVC exposure. RESULTS: It was confirmed that inhibition of tyrosine kinase activation reduces the survival of UV-irradiated HeLa S3 cells. However, no effect was seen on the survival of either NCTC 2544 human keratinocytes or A431 human epidermal carcinoma cells. In contrast, specific inhibition of PKC reduced the survival of UV-irradiated keratinocytes but had no effect on HeLa cells. Comparison of the effects of different inhibitors in keratinocytes suggested that this effect was mediated mostly through PKCmu and PKClambda/iota. In addition, keratinocyte exposure to UVC induced large and temporally distinct increases in PKCmu and PKClambda/iota. CONCLUSIONS: The survival of NCTC 2544 keratinocytes, but not HeLa S3 cells, following UVC exposure is mediated by signalling through PKC, mostly PKCmu and PKClambda/iota. Further study is required to confirm these results in normal human keratinocytes.

Carcinoma, Squamous Cell↗

IR spectroscopic characteristics of cell cycle and cell death probed by synchrotron radiation based Fourier transform IR spectromicroscopy.

Synchrotron radiation based Fourier transform IR (SR-FTIR) spectromicroscopy allows the study of individual living cells with a high signal to noise ratio. Here we report the use of the SR-FTIR technique to investigate changes in IR spectral features from individual human lung fibroblast (IMR-90) cells in vitro at different points in their cell cycle. Clear changes are observed in the spectral regions corresponding to proteins, DNA, and RNA as a cell changes from the G(1)-phase to the S-phase and finally into mitosis. These spectral changes include markers for the changing secondary structure of proteins in the cell, as well as variations in DNA/RNA content and packing as the cell cycle progresses. We also observe spectral features that indicate that occasional cells are undergoing various steps in the process of cell death. The dying or dead cell has a shift in the protein amide I and II bands corresponding to changing protein morphologies, and a significant increase in the intensity of an ester carbonyl C===O peak at 1743 cm(-1) is observed. Biopolymers (Biospectroscopy) 57: 329-335, 2000

Cell Cycle↗

Reactivities of flavonoids with different hydroxyl substituents for the cleavage of DNA in the presence of Cu(II).

DNA strand scission reactions of flavonoids in the presence of Cu(II) have been extended by using flavonoids with a variety of patterns of hydroxyl substitution. In particular we have examined for the first time a flavonoid (7,8-dihydroxyflavone) that lacks the possibility of forming a complex involving the oxygen at position 4. By comparing the reactivities of several flavonoids, including data from the literature, we draw generalizations for the correlation of structure and activity and present evidence for at least three different modes of action of flavonoids as genotoxic agents.

Copper↗

Ovarian carcinoma of low malignant potential treated at the Jewish General Hospital, Montreal, between 1973 and 1997.

OBJECTIVE: To review the epidemiologic and pathological characteristics and the management of ovarian cancer of low malignant potential (LMP) at a university teaching institution. DATA SOURCE: Hospital charts from 1973 to 1997. DATA EXTRACTION: The authors carried out a manual study of the individual hospital charts covering the study period. DATA SYNTHESIS: The findings of this review revealed that the mean age of the 30 women in the study was 48.7 years and was similar in the subgroups of women having serous (18) and mucinous (9) types. In those women for whom staging information was available, all had either stage I disease (12 serous, 7 mucinous) or stage III disease (4 serous, 1 mucinous). Treatment consisted of: total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) with or without omentectomy (OM); BSO, unilateral oophorectomy or ovarian cystectomy alone; or TAH, OM and left salpingo-oophorectomy in women with stage I tumours. All women with stage III tumours underwent TAH, BSO and OM. The recurrence rate was low. Only 1 of 22 stage I tumours but 3 of 5 stage III tumours recurred. CONCLUSIONS: Appropriate postoperative treatment for women with this type of ovarian cancer should be conservative. However, the management of higher stage disease remains controversial.

Adult↗

Androgens and masculinization of genitalia in the spotted hyaena (Crocuta crocuta). 1. Urogenital morphology and placental androgen production during fetal life.

According to common understanding of sexual differentiation, the formation and development of a penile clitoris in female spotted hyaenas requires the presence of naturally circulating androgens during fetal life. The purpose of the present study was to determine potential source(s) of such fetal androgens by investigating the timing of urogenital development and placental production of androgen during early and mid-gestation. Fetuses determined to be female by molecular techniques (lack of SRY gene) at days 33 and 48 of gestation had undifferentiated gonads, but the clitoris was already 'masculinized' and was generally similar to the phallus of a 50-day-old male fetus. Wolffian and Müllerian ducts terminated at the urogenital sinus in both sexes and a urethra was present along the entire length of the clitoris and penis. The adrenal gland was large and histologically differentiated at 33 days. Steroid gradients across the uterus (a drop in delta 4-androstenedione, with increases in oestrogen and androgen), and high androstenedione in ovarian veins indicated that ovarian androstenedione was metabolized and secreted as testosterone by the placenta throughout gestation. In vitro, whole or homogenized placentae at days 48 and 58 of gestation (110 days total) metabolized radiolabelled androstenedione into testosterone and oestradiol; the specific enzymatic activity of early placental tissues was higher than at later stages. A human placental homogenate had higher aromatase activity but did not produce testosterone unless aromatase was inhibited. Infusion of labelled androstenedione into the uterine arteries of hyaenas demonstrated the conversion of this substrate into testosterone and oestradiol and their secretion into the fetal circulation. Evidently, androgen is produced by the placenta and secreted into the fetal circulation from early in pregnancy when masculinization is first evident, before differentiation of the fetal ovary.

Androgens↗

Hyperreactio luteinalis differentiated from severe ovarian hyperstimulation syndrome in a spontaneously conceived pregnancy.

The clinical presentation of hyperreactio luteinalis can mimic ovarian hyperstimulation. Historically, though, the former most often leads to unnecessary surgery whereas the latter is treated supportively. We present a case of a 32-year-old woman who was initially seen with markedly enlarged multicystic ovaries, ascites, and pleural effusions in the tenth week of a spontaneously conceived gestation. Despite a noniatrogenic cause, the patient received supportive management, as would be given with ovarian hyperstimulation syndrome. Making the distinction between hyperreactio luteinalis and ovarian hyperstimulation syndrome has important consequences for diagnosis and management.

Adult↗

A glgC gene essential only for the first of two spatially distinct phases of glycogen synthesis in Streptomyces coelicolor A3(2).

By using a PCR approach based on conserved regions of ADP-glucose pyrophosphorylases, a glgC gene was cloned from Streptomyces coelicolor A3(2). The deduced glgC gene product showed end-to-end relatedness to other bacterial ADP-glucose pyrophosphorylases. The glgC gene is about 1,000 kb from the leftmost chromosome end and is not closely linked to either of the two glgB genes of S. coelicolor, which encode glycogen branching enzymes active in different locations in differentiated colonies. Disruption of glgC eliminated only the first of two temporal peaks of ADP-glucose pyrophosphorylase activity and glycogen accumulation and prevented cytologically observable glycogen accumulation in the substrate mycelium of colonies (phase I), while glycogen deposition in young spore chains (phase II) remained readily detectable. The cloned glgC gene therefore encodes an ADP-glucose pyrophosphorylase essential only for phase I (and it is therefore named glgCI). A second, phase II-specific, glgC gene should also exist in S. coelicolor, though it was not detected by hybridization analysis.

Amino Acid Sequence↗

Adjunctive growth hormone during ovarian hyperstimulation increases levels of insulin-like growth factor binding proteins in follicular fluid: a randomized, placebo-controlled, cross-over study.

GH increases circulating insulin-like growth factor I (IGF-I), which can promote the growth and differentiated function of ovarian granulosa and theca cells. Reported studies of GH as an adjunct to menotropin stimulation in women, largely those with ovarian dysfunction, have not consistently shown a benefit of GH, despite increases in serum and follicular fluid IGF-I. We hypothesized that changes in intrafollicular IGF-binding proteins (IGFBPs), which can antagonize IGF actions on granulosa cells, may underlie the inconsistent effects of GH. In the present study of GH, administered in double-blind, placebo-controlled, cross-over fashion to regularly cycling women undergoing in vitro fertilization, we found that follicular fluid levels of IGFBP-1, -3, and -4 and serum levels of IGFBP-3, as well as follicular fluid and serum IGF-I, were significantly increased in the GH-treated cycles, when compared with the placebo cycle of the same patient. We suggest that the net increase in intrafollicular IGFBPs in GH cycles may mitigate the potential beneficial effect of increased IGF-I.

Adult↗

Characteristics of chief complaints of patients with temporomandibular disorders in a Brazilian population.

A retrospective survey of 894 patients with temporomandibular disorders was conducted in order to analyse the characteristics of chief complaints. The patients presented complaints of pain (82.1%), functional disturbance (12.3%), articular sounds (5.0%) and swelling (0.6%). Unilateral occurrence (66.5%) was more frequent than bilateral. The most frequent location of pain was the temporomandibular joint (TMJ) (82.1%) followed by ear (10.8%), face (2.3%), head (2.3%), mandible (1.0%), neck (0.9%), temporal (0.4%) and frontal (0.1%) areas. Pain in the TMJ occurred in isolation (87.9%) or associated to other locations. The most frequent functional disturbance was limitation of jaw opening (32.1%).

Adolescent↗

Assisted reproductive technologies: estimates of their contribution to multiple births and newborn hospital days in the United States.

OBJECTIVE: Estimate the contribution of assisted reproductive technology (ART) in the United States to multiple gestation births and newborn hospital days. DESIGN: Analysis of successful ART conceptions occurring during 1990 to 1991 compared with vital statistics. Newborn hospital days are estimated from the 1990 National Hospital Discharge Survey. SETTING: The American Fertility Society and the Society for Assisted Reproductive Technology registry. PATIENTS: Infants delivered from ART. INTERVENTIONS: Assisted reproductive technology. MAIN OUTCOME MEASURES: Number of multiple gestation infants and newborn hospital days. RESULTS: Approximately 12,327 live-born infants were delivered from ART conceptions during 1990 to 1991, representing 22.2% of all live-born triplet, 17.3% of quadruplet, and 11.4% of quintuplet infants born in the United States. The number of newborn hospital days attributed to ART infants was 87,135 days. Between the periods 1972 through 1974 and 1990 through 1991, the rate of triplet and higher order multiple gestation infants per 100,000 white live births increased by 191%, with 38% due to ART conceptions and 30% to increased childbearing among older women. CONCLUSIONS: Assisted reproductive technology contributed 22% of U.S. triplet and higher order multiple births during 1990 to 1991.

Female↗

Functional maturation of the primate fetal adrenal in vivo: I. Role of insulin-like growth factors (IGFs), IGF-I receptor, and IGF binding proteins in growth regulation.

The rapid growth of the primate fetal adrenal from midgestation until term is regulated by ACTH secreted by the fetal pituitary. Previous studies suggest that the trophic actions of ACTH are mediated by insulin-like growth factor II (IGF-II) synthesized by fetal adrenal cortical cells. To characterize further the role of IGF-II in the regulation of fetal adrenal growth, we investigated the expression of the messenger RNAs (mRNAs) encoding IGF-I, IGF-II, IGF-I receptor (IGF-IR) and IGF binding protein (IGFBP) 1-6 in the fetal rhesus monkey adrenal in vivo from 109 days of gestation until term (165 +/- 5 days) using in situ hybridization. To assess the role of ACTH in the regulation of expression of the IGF system in vivo, we administered metyrapone (3-7 days) to late gestation fetal rhesus monkeys (n = 4) in utero to increase fetal pituitary ACTH secretion. IGF-II mRNA was abundant in the definitive, transitional and fetal zones of the adrenal cortex from 109 days until term. IGF-IR mRNA was expressed in the definitive, transitional and fetal zones and decreased to nondetectable levels at term. IGFBP-2 and IGFBP-6 mRNAs were expressed in the definitive, transitional, and fetal zones, whereas IGFBP-1, -3, -4, and -5 were not detected in adrenal cells. The effects of increasing ACTH secretion on the growth of the specific zones of the adrenal were determined using morphometric techniques. Metyrapone treatment approximately doubled adrenal weight, which was due to an increase in the area of the definitive, transitional, and fetal zones with decreased cell density of the definitive, transitional, and fetal zones compared with controls and not due to a change in total cell number. Therefore, the increase in adrenal weight after metyrapone treatment was due to hypertrophy of the three cortical zones; there was no effect on adrenal medullary growth. The relative abundance of the mRNAs encoding IGF-II and the IGF-IR was increased after metyrapone treatment, whereas the localization and relative abundance of IGFBP 1-6 mRNAs were not altered by metyrapone treatment. We conclude that the ontogenetic increase in adrenal growth may be regulated, at least in part, by locally synthesized IGF-II, and the cessation of adrenal growth that occurs at term may be mediated by the decrease in the IGF-IR. The adrenal cortical expression of IGFBP-2 and IGFBP-6 suggests that these IGFBPs may modulate the IGF-IGF-IR interaction. Metyrapone treatment, which likely increased fetal pituitary ACTH secretion, causes a coordinated increase in expression of IGF-II and IGF-IR in fetal adrenal cortical cells, which may be an important mechanism of regulation of fetal adrenal cortical growth.

Adrenal Glands↗

Functional maturation of the primate fetal adrenal in vivo. II. Ontogeny of corticosteroid synthesis is dependent upon specific zonal expression of 3 beta-hydroxysteroid dehydrogenase/isomerase.

Cortisol, produced by the primate fetal adrenal, regulates the maturation of organ systems necessary for extrauterine life. During most of primate pregnancy, however, the fetal adrenal lacks the enzyme 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta HSD), which is essential for cortisol synthesis. Therefore, we used immunohistochemistry and in situ hybridization techniques to investigate the developmental expression of 3 beta HSD in the fetal rhesus monkey adrenal from 109 days' gestation until term (165 +/- 5 days) and assessed the role of ACTH in the induction of its expression and localization. We also examined whether ACTH regulates the expression of two other steroidogenic enzymes, cytochrome P450 cholesterol side-chain cleavage (P450scc) and P450 17 alpha-hydroxylase, 17/20-lyase (P450c17), in the fetal rhesus monkey adrenal. To stimulate ACTH secretion from the fetal pituitary in vivo, we administered metyrapone to late gestation fetal rhesus monkeys for 3-7 days. Adrenals were collected from untreated fetuses at 109-125 days (n = 5), 130-148 days (n = 7), 155-172 days (n = 4), and after metyrapone treatment at 135-137 days (n = 4). The cortical width and total amount of 3 beta HSD staining were measured using an image analysis system. 3 beta HSD was localized primarily in the definitive zone cells of the adrenal from fetuses between 109-148 days, whereas at term (155-172 days), 3 beta HSD was localized in both definitive and transitional zone cells. The cortical width and total amount of 3 beta HSD staining in the adrenal increased significantly (P < 0.05) between 148 days (137 +/- 14 microns and 3,689 +/- 522 grains) and 155 days (315 +/- 61 microns and 7,321 +/- 2,008 grains). Interestingly, in metyrapone-treated fetuses at 135-137 days, 3 beta HSD messenger RNA (mRNA) and protein were localized extensively in both the definitive and transitional zones, a pattern seen only in term fetal adrenals in untreated animals. In addition, metyrapone treatment significantly (P < 0.05) increased cortical width (386 +/- 95 microns) and total 3 beta HSD immunostaining (29,063 +/- 13,692 grains) compared with age-matched controls. In contrast to 3 beta HSD, P450scc mRNA was detected in the definitive, transitional, and fetal zones, and its expression was not altered after metyrapone treatment. P450c17 mRNA was detected in the transitional and fetal zones, and the relative abundance was greater in the transitional zone. The relative abundance of P450c17 mRNA was increased in the fetal zone after metyrapone treatment. In summary, at term or after metyrapone treatment, expression of 3 beta HSD is induced in the transitional zone of the fetal rhesus monkey adrenal gland, an indication of functional maturation of the primate adrenal cortex. These data suggest that the ontogenetic increase in fetal pituitary ACTH secretion plays an important role in the induction of 3 beta HSD expression in the transitional zone.

Adrenal Cortex Hormones↗

Transjugular intrahepatic portosystemic shunt with the Strecker stent for control of refractory acute and chronic variceal bleeding.

BACKGROUND: We wanted to assess prospectively the safety, efficacy, and applicability of transjugular intrahepatic portosystemic shunt (TIPS) with the Strecker stent, focusing mainly on clinical and hemodynamic medium- and long-term follow-up. METHODS: Fifty-two patients reached an indication to perform a TIPS, in an emergency or after refractory variceal bleeding. It was completed in 50 of them. All presented with cirrhosis (Child C = 15, B = 23, A = 12). The prosthesis was a Strecker stent. During the follow-up, clinical, biochemical, endoscopic, ultrasound, and pressure measurement studies were performed at 1, 3, 6, 12 months. Mean follow-up was 13.5 + or - 7.8 months. RESULTS: Portal pressure decreased from 32.3 + or - 8.1 (mean + or - standard deviation) to 22.3 + or - 6.7 mm Hg and portocaval gradient from 21 +/- 5.2 to 8.7 +/- 3.9 mm Hg (average, 56 + or - 16%). Shunt dysfunction was diagnosed when the portocaval gradient was >12 mm Hg (20 patients). Eleven patients (22%) presented with variceal rebleeding because of shunt dysfunction. The probability of remaining free of bleeding was 78%, 74%, and 68% at 6, 12, and 24 months, respectively. Actuarial survival rate was 91% and 86% after 12 and 18 months, respectively. CONCLUSION: TIPS with the Strecker stent is a safe alternative for variceal bleeding. Shunt dysfunction is frequent and increases the rebleeding rate, requiring a close follow-up with pressure measurements. Randomized trials comparing stents and other alternatives are needed to fully address the role of this procedure.

Acute Disease↗

The choice of a gonadotropin-releasing hormone analog influences outcome of in vitro fertilization treatment.

OBJECTIVE: Our purpose was to determine if there is a difference in outcome associated with choice of gonadotropin-releasing hormone analog in in vitro fertilization treatment cycles. STUDY DESIGN: A retrospective analysis of 510 consecutive in vitro fertilization cycles with patient-selected use of either nafarelin (Synarel) or leuprolide (Lupron) was performed. RESULTS: Of 510 consecutive patient cycles, 284 patients (56%) chose nafarelin and 226 (44%) chose leuprolide. In the nafarelin group 64 cycles (34% of retrievals) resulted in deliveries. In the leuprolide group 37 (24%) resulted in delivery (p < 0.05). There were 260 patients in their first cycle of treatment, with 157 (60%) choosing nafarelin, resulting in 33 deliveries (34% per retrieval). Leuprolide, used in 103 (40%) of first cycles, resulted in 12 deliveries (20% per retrieval), (p = 0.052). CONCLUSIONS: In a large population of unselected patients undergoing in vitro fertilization the choice of nafarelin was associated with a significantly better outcome in terms of successful pregnancies achieved.

Adult↗