Search PubMed⌕ Search

Biomedical subjects

J R Jacobs

Publications and source records attributed to J R Jacobs.

At least 37 records · Page 2Linked to original sources
PubMed1998

The expression of MDP-1, a component of Drosophila embryonic basement membranes, is modulated by apoptotic cell death.

Using a novel monoclonal antibody we have studied the expression of a large proteoglycan-type molecule in Drosophila embryos. This molecule is secreted exclusively by migratory, embryonic hemocytes/macrophages and was therefore named MDP-1 for Macrophage-Derived Proteoglycan-1. Expression of MDP-1 begins late during hemocyte differentiation, after these cells have left their birthplace in the head mesoderm. At this time, macrophages are engaged in extracellular matrix deposition and the phagocytosis of cell debris generated by apoptotic events in various parts of the embryo, in particular from the developing central nervous system. Embryos deficient for programmed cell death display a greatly reduced amount of MDP-1 deposition in tissues that normally undergo morphogenetic cell death. This suggests a regulatory role for apoptosis in the terminal differentiation of Drosophila hemocytes. MDP-1 is initially deposited around the developing central nervous system and is later found in basement membrane structures surrounding various other organs, such as the gut, Malpighian tubules and part of the tracheal system. The temporal and localized deposition of MDP-1 suggests that it may play a role in delineating the central nervous system structure during axonogenesis and may participate in the formation of a functional 'blood-brain barrier' in Drosophila.

Animals↗
PubMed1997

Origin and differentiation of supernumerary midline glia in Drosophila embryos deficient for apoptosis.

Drosophila embryos deficient for programmed cell death produce 9 midline glia (MG) in addition to the wild-type complement of 3.2 MG/segment. More than 3 of the supernumerary MG derive from the MGP (MG posterior) lineage and the remainder from the MGA/MGM (MG anterior and middle) lineage. There is one unidentified additional neuron in the mesectoderm of embryos deficient for apoptosis. The supernumerary MG are not diverted from other lineages nor do they arise from an altered pattern of mitosis. Instead, these MG appear to arise from a normally existing pool of 12 precursor cells, larger than anticipated by earlier studies. During normal development, MG survival is dependent upon signaling to the Drosophila EGF receptor. The persistence of supernumerary MG in embryos deficient for apoptosis does not alter the spatial pattern of Drosophila EGF receptor signaling. The number and position of MG which express genes dependent upon EGF receptor function, such as pointed or argos, are indistinguishable from wild type. Genes of the spitz group are required for Drosophila EGF receptor function. Surviving MG in spitz group/H99 double mutants continue to express genes characteristic of the MG, but the cells fail to differentiate into ensheathing glia and are displaced from the nerve cord.

Animals↗
PubMed1997

Argos and Spitz group genes function to regulate midline glial cell number in Drosophila embryos.

The midline glia of the Drosophila embryonic nerve cord undergo a reduction in cell number after facilitating commissural tract morphogenesis. The numbers of midline glia entering apoptosis at this stage can be increased by a loss or reduction of function in genes of the spitz group or Drosophila EGF receptor (DER) pathway. Argos, a secreted molecule with an atypical EGF motif, is postulated to function as a DER antagonist. In this work, we assess the role of argos in the determination of midline glia cell number. Although all midline glia express DER, argos expression is restricted to the midline glia which do not enter apoptosis. Fewer midline glia enter apoptosis in embryos lacking argos function. Ectopic expression of argos is sufficient to remove all DER-expressing midline glia from the nerve cord, even those that already express argos. DER expression is not terminated in the midline glia after spitz group signaling triggers changes in gene expression. It is therefore likely that an attenuation of DER signaling by Argos is integrated with the augmentation of DER signaling by Spitz throughout the period of reduction of midline glia number. We suggest that signaling by Spitz but not Argos is restricted to adhesive junctions. In this manner, midline glia not forming signaling junctions remain sensitive to juxtacrine Argos signaling, while an autocrine Argos signal is excluded by the adhesive junction.

Animals↗
PubMed1996

Mutations in the gene stand still disrupt germ cell differentiation in Drosophila ovaries.

During oogenesis in Drosophila, germ cells appear in sequential clusters of 16 interconnected cells. The events surrounding the differentiation of these cells are not fully understood. Here we present genetic and morphological analysis of mutations in the gene stand still (stil). Through complementation analyses we have refined the location of this gene to cyological region 49B-C. Our analyses of ovaries from ethylmethane sulfonate (EMS)-induced mutant alleles of this gene suggest that mutations in the stil gene produce a wide range of phenotypic abnormalities, from the absence of germ cells in the most severe alleles, to egg chambers with cytoskeletal defects in the less severe alleles. Our results suggest a role for this gene in specifying or maintaining a cytoskeletal component, with consequences during oogenesis and possibly during germ line sex determination.

Actins↗
PubMed1996

Selenate fortification of infant formulas improves the selenium status of preterm infants.

The purpose of this study was to determine whether selenate fortification of infant formula would improve the selenium status of relatively well, growing, preterm infants during the first 12 wk of enteral feeding. A high-selenium group (n = 7, mean body weight = 1312 g) received selenate-fortified preterm and full-term infant formulas containing 0.36 and 0.22 mumol Se/L, respectively, and a low-selenium group (n = 10, mean body weight = 1262 g) received non-selenium-fortified preterm and full-term infant formulas containing 0.12 and 0.11 mumol Se/L, respectively. There were no significant differences in growth between the two groups throughout the study. The high-selenium group had significantly greater mean selenium intakes than did the low-selenium group from weeks 2 to 12. Plasma selenium concentrations decreased over the study period in the low-selenium group. Plasma selenium-dependent glutathione peroxidase activity was greater in the high-selenium group at week 12 only. Red blood cell selenium concentrations decreased over time in both groups and were significantly greater in the high-selenium group at weeks 4, 8, and 12. Plasma selenium concentrations were significantly correlated with plasma glutathione peroxidase activity for all infants on study day 1 and at weeks 4 and 12. Selenium intake of all infants was significantly correlated with plasma glutathione peroxidase activity at 12 wk. Selenate fortification of infant formulas can improve the selenium status of preterm infants. Current selenium contents of infant formulas and recommendations for dietary intakes of selenium for some preterm infants may be inadequate.

Anthropometry↗
PubMed1996

Outcome of pyriform sinus cancer: a retrospective institutional review.

Pyriform sinus cancer remains one of the most lethal of human diseases. Regardless of approach attempted significant enhancement of survival has not been realized. In this study a retrospective single institutional review of all patients diagnosed with pyriform sinus cancer during the 1980s was conducted. The results in 93 patients show an overall determinant 5-year survival of 14.3%. Of patients undergoing surgery, median determinant survival was 37 months and 5-year survival was 34.6%. In resectable patients treated with radiation with or without chemotherapy, median determinant survival was 13 months with 5-year survival of 7.1% (P < .01). Surgical salvage was attempted in 8 patients without success. In conclusion, due to the apparent survival advantage for surgical patients, the low rate of surgical salvage, and the relatively low rate of organ preservation in prospective trials, pyriform sinus cancer is a poor site for organ preservation. Surgery followed by radiation therapy should remain the standard of care for pyriform sinus cancer.

Aged↗
PubMed1995

Macrophages and glia participate in the removal of apoptotic neurons from the Drosophila embryonic nervous system.

Cell death in the Drosophila embryonic central nervous system (CNS) proceeds by apoptosis, which is revealed ultrastructurally by nuclear condensation, shrinkage of cytoplasmic volume, and preservation of intracellular organelles. Apoptotic cells do not accumulate in the CNS but are continuously removed and engulfed by phagocytic haemocytes. To determine whether embryonic glia can function as phagocytes, we studied serial electronic microscopic sections of the Drosophila CNS. Apoptotic cells in the nervous system are engulfed by a variety of glia including midline glia, interface (or longitudinal tract) glia, and nerve root glia. However, the majority of apoptotic cells in the CNS are engulfed by subperineurial glia in a fashion similar to the microglia of the vertebrate CNS. A close proximity between macrophages and subperineurial glia suggests that glia may transfer apoptotic profiles to the macrophages. Embryos affected by the maternal-effect mutation Bicaudal-D have no macrophages. In the absence of macrophages, most apoptotic cells are retained at the outer surfaces of the CNS, and subperineurial glia contain an abundance of apoptotic cells. Some apoptotic cells are expelled from the CNS, which suggests that the removal of apoptotic cells can occur in the absence of macrophages. The number of subperineurial glia is unaffected by changes in the rate of neuronal apoptosis.

Animals↗
PubMed1995

Compartment model to describe peripheral arterial-venous drug concentration gradients with drug elimination from the venous sampling compartment.

The central compartment of an n-compartment mammillary model was concatenated with a gradient compartment (i.e., venous sampling compartment) and with a conventional effect compartment to model arterial-venous drug concentration gradients and the arterial drug concentration vs effect relationship, respectively. To model drug metabolism during transit between the peripheral arterial and peripheral venous circulations, the gradient compartment included a first-order elimination path. Simulations of the model were employed to demonstrate the impact of sampling site (e.g., arterial vs peripheral venous) on analyses of the concentration vs effect relationship.

Arteries↗
PubMed1995

Bipedicle delayed flap closure of persistent radiated tracheocutaneous fistulas.

Increasing numbers of patients have had tracheostomies for prolonged periods of time and when subsequently decannulated have developed persistent tracheocutaneous fistula. A substantial percentage of these patients have undergone successful combined modality therapy excluding surgery for advanced head and neck cancer with resulting healing deficits of the remaining tissues. Although these patients may be deemed suitable for decannulation at this particular point, the potential still exists that access to the trachea will be required sometime in the future. This situation requires a method of closure that is reasonably reliable and yet, at the same time, relatively easily reversible. The surgical technique presented appears to meet these demands. After primary inversion of the edges of the tracheocutaneous fistula, a bipedicle flap is developed and positioned over the tracheostomy site. The inferior edge of the flap is left open for temporary air escape to decompress the suture line. This line subsequently heals by secondary intention over the succeeding weeks. Although there has not been, to date, the need to reverse the closure, the relative thinness of the tissue as opposed to alternative techniques suggests that it should not be difficult.

Cutaneous Fistula↗
PubMed1995

Lectin histochemistry of the Drosophila embryo.

A selection of lectins was used to characterise changes in the distribution of glycoconjugates during the embryonic development of Drosophila melanogaster. The blastoderm of pre-gastrulation embryos bound low levels of the lectins LPA, UEA-I and PNA. The germ line progenitors (pole cells) bound ConA, PNA and LPA. The yolk granules, the trachea, and the gut bound GSA-I. All lectins had detectable labeling of the ectoderm. The somata of the nervous system bound ConA and LPA. Electron microscopic analysis of PNA labeling of the nervous system revealed exclusive binding to the axon tracts and ensheathing glia. Hyaluronate lyase digestion of oligosaccharides revealed gut and nervous system binding with WGA and UEA-I. This study revealed useful biochemical probes of gut, epidermal and nervous system development that identify the distribution of likely ligands for as yet uncharacterised endogenous lectins.

Animals↗
PubMed1995

Sinus disease in the bone marrow transplant population: incidence, risk factors, and complications.

BACKGROUND: Fever associated with sinus disease in the immunocompromised bone marrow transplant recipient requires prompt evaluation and therapy. Very little is known about the incidence, risk factors, and sequelae of nonsurgically treated sinus disease in this population. METHODS: A retrospective review of 107 consecutive allogeneic and autologous bone marrow transplant recipients from August 1987 to July 1989 was performed to determine (1) the overall incidence of sinus disease; (2) factors that influence the development of sinus disease; and (3) the sequelae of sinus disease treated nonsurgically. RESULTS: Overall 33 (31%) of 107 bone marrow transplant recipients had sinus disease defined as a radiographic abnormality with clinical symptoms. Eleven (10%) of 107 recipients had preexisting sinus disease. Sinus disease developed in 22 (21%) of 107 recipients after bone marrow transplantation. Sinus abnormalities were significantly higher among allografted bone marrow transplant recipients than among autografted recipients (p = 0.027). The diagnosis, stage of disease, cytoreductive regimen, or graft-vs.-host disease were not different between recipients in whom sinus disease did and did not develop. There were no deaths as a result of sinus complications. CONCLUSIONS: Sinus disease developed in 21% of the studied population after bone marrow transplantation. Allogeneic recipients had a higher incidence of sinus disease than autologous recipients. There were no deaths attributed to sinus complications. All sinus disease in this bone marrow transplant population was treated medically. No patient required surgical intervention either before or after bone marrow transplantation.

Adult↗
PubMed1995

Ameloblastic carcinoma of the maxilla.

Ameloblastic carcinoma is an unusual tumour. There have been a total of 34 cases of ameloblastic carcinoma in the English literature to date. Of these only 11 cases have occurred in the maxilla. The authors report the 12th such case. The histological classification for odontogenic carcinoma has been debated for many years and recently revised, thus differentiating between malignant ameloblastoma and ameloblastic carcinoma. The authors review the current literature regarding diagnosis and treatment of this unusual lesion, and support the use of the term malignant ameloblastoma for the tumours that metastasize in spite of their benign histological appearance, whereas, the ameloblastic carcinoma is referred to as the primary tumour with malignant transformation, regardless of its metastatic potential.

Aged↗
PubMed1995

Aging increases pharmacodynamic sensitivity to the hypnotic effects of midazolam.

The effect of aging on the pharmacodynamics of midazolam was investigated in a double-blinded study involving 39 consenting patients ranging in age from 39 to 77 yr. Midazolam was infused intravenously (i.v.) using a pharmacokinetic model-driven drug infusion device to achieve a plasma midazolam concentration that was held constant for the 10-min duration of the study. Blood samples were obtained from the radial artery at 5 and 10 min for subsequent measurement of the plasma midazolam concentrations. With the 10-min sample, the patients were also assessed for the presence or absence of responsiveness to verbal command. To ensure that the pharmacodynamic end-point was assessed under the condition of a relative steady-state effect-site midazolam concentration, only those patients (n = 33) in whom the plasma midazolam concentration at 10 min was within 30% of the measured concentration at 5 min were included in the subsequent data analyses. Logistic regression was used to fit the verbal command response/no response data to a mathematical model that included patient age and the plasma midazolam concentration measured at 10 min. Cp50, the steady-state plasma midazolam concentration at which 50% of patients would be expected not to respond to a specific stimulus (e.g., verbal command), was calculated as a function of age from the parameterized logistic model. The midazolam Cp50 for response to verbal command decreased significantly (P = 0.034) with increasing patient age, demonstrating that aging increases pharmacodynamic sensitivity to the hypnotic effects of midazolam independent of pharmacokinetic factors.

Adult↗
PubMed1995

Measured context-sensitive half-times of remifentanil and alfentanil.

BACKGROUND: The context-sensitive half-time, rather than the terminal elimination half-life, has been proposed as a more clinically relevant measure of decreasing drug concentration after a constant infusion of a given duration. The context-sensitive half-time is derived from computer modelling using known pharmacokinetic parameters. The modelled context-sensitive half-time for a 3-h infusion of alfentanil is 50-55 min and is 3 min for remifentanil. The terminal elimination half-life is 111 min for alfentanil and 12-30 min for remifentanil. It has not been tested whether the modelled context-sensitive half-time reflects the true time for a 50% decrease in drug concentration or drug effect. METHODS: Thirty volunteers received a 3-h infusion of remifentanil or alfentanil at equieffective concentrations. Depression of minute ventilation to 7.5% ETCO2 was used as a measure of drug effect. Minute ventilation response was measured, and blood samples for drug concentration were taken during and after drug infusion. The recovery of minute ventilation (drug effect) and decrease in blood drug concentration was plotted, and the time for a 50% change was determined. RESULTS: The measured pharmacokinetic context-sensitive half-time for remifentanil after a 3-h infusion was 3.2 +/- 0.9 min, and its pharmacodynamic offset was 5.4 +/- 1.8 min. Alfentanil's measured pharmacokinetic context-sensitive half-time was 47.3 +/- 12 min, and its pharmacodynamic offset was 54.0 +/- 48 min. The terminal elimination half-life modelled from the volunteers was 11.8 +/- 5.1 min for remifentanil and 76.5 +/- 12.6 min for alfentanil. CONCLUSIONS: The measured context-sensitive half-times were in close agreement with the context-sensitive half-times previously modelled for these drugs. The results of this study confirm the value of the context-sensitive half-time in describing drug offset compared to the terminal elimination half-life.

Adult↗
PubMed1995

Fortification of human milk: evaluation of a novel fortification scheme and of a new fortifier.

Human milk fed to very-low-birth-weight infants must be fortified with protein, minerals, and vitamins. We tested a new fortification regimen in which the amount of fortifier was adjusted on the basis of frequent determinations of serum urea nitrogen (SUN). A newly formulated fortifier based on bovine milk proteins was employed either in the new fashion (regimen ADJ) or in the conventional fixed proportion (regimen FIX). Using the fixed proportion, the study also compared the new fortifier with a fortifier based on human milk protein (regimen HMP). Twelve infants were studied with each of the three regimens; nearly all completed 3 weeks of study. Protein intake was generally higher in ADJ than FIX; the difference was significant (p < 0.01) during week 2. Weight gain was somewhat (but not significantly) greater in regimen ADJ (32.3 g/d or 18.8 g/kg/d) than in regimen FIX (30.0 g/d or 18.3 g/kg/d). SUN was higher in ADJ than in FIX, and several other serum chemical values (calcium, phosphorus, potassium) tended to be higher, probably reflecting higher intakes of these nutrients with ADJ than with FIX. Plasma concentrations of several amino acids were higher in ADJ than FIX, but none, including threonine, were outside the physiological range. In comparing regimen FIX to regimen HMP, infants on FIX received similar intakes of protein and showed slightly but not significantly more rapid weight gain. Concentrations of SUN were lower with FIX, but other serum chemical values, including amino acids, were generally similar to HMP. We conclude that use of the new adjustable fortification regimen is feasible and safe and that it should be studied further. It produced the expected increases in nutrient intakes and growth. The new bovine milk-based fortifier appears to be equivalent to the human milk-based fortifier.

Amino Acids↗