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Biomedical subjects

S Busch

Publications and source records attributed to S Busch.

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

Growth factor-like action of lysophosphatidic acid on human B lymphoblasts.

Proliferation and immunoglobulin secretion of B lymphocytes are regulated by specific antigens and numerous accessory immunomodulatory factors. Lysophosphatidic acid (LPA) is a glycerophospholipid mediator that is released from activated blood platelets, attains high levels in serum, and exerts potent stimulatory effects on, e.g., neutrophils, monocytes, and T lymphocytes. LPA is also generated by a secretory, cytokine-inducible phospholipase A2 present in high concentrations in inflammatory exudates and septic states. We investigated effects of LPA on human Epstein-Barr virus-immortalized B lymphoblasts, a model for immunoglobulin-secreting B cells. Intracellular Ca2+ was determined with fura 2 and the formation of inositol 1,4, 5-trisphosphate by anion-exchange chromatography. LPA stimulated an increase in inositol 1,4,5-trisphosphate levels and induced a transient rise in intracellular free Ca2+ concentration from 105 +/- 17 to 226 +/- 21 nM. This Ca2+ signal resulted from Ca2+ mobilization and Ca2+ influx and was subject to homologous desensitization. Pertussis toxin inhibited these responses by approximately 70%. Furthermore, LPA stimulated a 27.5% increase in guanosine 5'-O-(3-thiotriphosphate) binding to permeabilized B lymphoblasts, which suggests the direct activation of pertussis toxin-sensitive G proteins by LPA. LPA stimulated a strong increase in the specific phosphorylation of the mitogen-activated protein kinase (immunoblot analysis) that was prevented by the MEK inhibitor PD-98059. Finally, LPA triggered a 2-fold increase in DNA synthesis ([3H]thymidine incorporation) and a 2-fold increase in B lymphoblast number and evoked a 20- to 50-fold increase in immunoglobulin formation. By RT-PCR we detected specific mRNA transcripts for the recently cloned human LPA receptor. Thus our data suggest that LPA behaves as a B cell growth factor.

Antibody Formation↗
PubMed1997

Cloning and sequencing of the cDNA encoding for a Na+/H+ exchanger from Xenopus laevis oocytes (X1-NHE).

We have cloned and sequenced the cDNA for a Na+/H+ exchanger (NHE) from Xenopus laevis oocytes. This cDNA contains an open reading frame encoding a protein of 782 amino acids with 12 putative transmembrane domains and a long cytoplasmic tail. The protein exhibits a strong homology at the amino acid level to the human NHE-1 as well as to the beta NHE from trout red blood cells: 69% and 58% respectively. Two potential N-linked glycosylation sites at Asn56 and Asn351 were identified. Three potential protein kinase C phosphorylation sites at the cytoplasmic tail were identified at Ser494, Thr726 and Ser747. RT-PCR revealed the expression of the X1-NHE in Xenopus heart, reticulocytes and skeletal muscle.

Amino Acid Sequence↗
PubMed1997

Carving-out mental health benefits to Medicaid beneficiaries: a shift toward managed care.

Several states have designed and implemented innovative programs for Medicaid beneficiaries that carve-out the provision of mental health from general health care. This paper describes several such programs and outlines the choices states face in designing these services. Major decisions include the selection of a public or private agency, how that agency is chosen, reimbursement schemes, eligibility criteria, and benefits to be covered. While carve-out programs have yielded initial savings, more research is needed on their effect on quality of care and general health care costs.

Contract Services↗
PubMed1997

Signalling properties of lysophosphatidic acid in primary human skin fibroblasts: role of pertussis toxin-sensitive GTP-binding proteins.

We have investigated the signalling properties of the naturally occurring intercellular signalling molecule lysophosphatidic acid (LPA) in primary human skin fibroblasts. LPA stimulated phospholipase C activity resulting in the formation of inositol 1,4,5-trisphosphate (IP3) which was accompanied by a concentration-dependent increase in intracellular calcium concentration ([Ca2+]i). The increase in [Ca2+]i was subject to homologous desensitisation but not to heterologous desensitisation by sphingosine-1-phosphate. The half-maximal effect of LPA on the rise in [Ca2+]i was attained at 7-20 nM. IP3 formation and Ca2+ mobilisation were highly pertussis toxin (PTX)-sensitive (100% and 75%, respectively). LPA also inhibited forskolin-stimulated formation of cAMP, which was partially reversed (51%) when fibroblasts were pretreated with PTX. To directly test the involvement of guanine nucleotide-binding regulatory proteins (G proteins), LPA-induced binding of the stable GTP analogue GTP gamma S was measured. LPA induced an increase in GTP gamma S binding, which was completely inhibited by PTX, implicating the involvement of Gi-type G proteins in LPA signalling. Furthermore, LPA increased DNA synthesis and cell proliferation. Finally, LPA induced the migration of human skin fibroblasts, which in conjunction with the stimulation of cell growth strengthens the presumed involvement of LPA in wound healing and tissue regeneration. Both effects (cell growth and migration) were almost completely PTX-sensitive. Overall, these investigations in primary cultures of human skin fibroblasts confirm and extend our knowledge about LPA signalling, suggesting a pivotal role of receptor coupled activation of Gi-type proteins at least in this cell type.

Calcium↗
PubMed1997

[Empirical analysis of work flow in inpatient nursing homes for the elderly].

The paper starts by offering a short overview of the state of implementation of the 2nd stage of the newly introduced German Long-Term-Care-Insurance (Pflegeversicherung). It continues to present results of a detailed descriptive analysis of employee activities in (long-term-care-)nursing-homes, differentiating by severity of the patients' condition. Surprisingly nurses spend a large part of their time (40%) on other than nursing activities. The time spent with individual patients varies considerably with sex and the main diagnosis; thus significantly more time is spent on (basic and treatment-related) nursing care for male patients. Age per se does not appear to influence the time required for taking care of a patient.

Aged↗
PubMed1997

[Day care as a component of comprehensive health care structure after introduction of nursing care insurance].

Detailed time protocols based on direct observation as well as socio-demographic and morbidity-related data were collected in Day-Care-Facilities for the Aged and the Handicapped (Tagespflege), in order to gain information regarding the users and the service activities of these institutions. Women aged 80 years and over constitute the main users; they use the facilities between 8 am and 4.30 pm in most cases. The analysis of employee activities showed that roughly one quarter of the time was spent on specific services of such facilities, e.g. group activities, individual activating therapy of patients. Should Day-Care-Facilities play an (increasingly) important role in the domestic social service provision for the aged and the handicapped, the financing of their costs (on the average DM 88 per day, not counting transportation cost) must be reconsidered.

Aged↗
PubMed1996

Selectively enhanced cellular signaling by Gi proteins in essential hypertension. G alpha i2, G alpha i3, G beta 1, and G beta 2 are not mutated.

Recent studies have shown an enhanced signaling capacity of receptors coupled to pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G proteins) in immortalized B lymphoblasts from patients with essential hypertension. In the present study, we analyzed (1) whether such alterations would also be expressed in nontransformed cells of these individuals and (2) whether other G protein-mediated signaling pathways were also altered. Therefore, we established primary cultures of skin fibroblasts from previously characterized normotensive and hypertensive individuals (NT and HT cells, respectively). [Ca2+]i rises induced by lyso-phosphatidic acid (LPA), thrombin, and sphingosine-1-phosphate as well as the formation of inositol 1,4,5-trisphosphate and [3H]thymidine incorporation evoked by LPA were PTX sensitive and enhanced twofold in HT fibroblasts. In contrast, cellular responses induced by bradykinin, endothelin-1, and angiotensin II (all PTX insensitive) were similar in NT and HT cells. Formation of cAMP induced by stimulation of Gs with isoproterenol was identical in NT and HT cells. Western blot analysis yielded no evidence for an overexpression of G alpha i2, G alpha i3, G beta 2, and G beta 4. Furthermore, sequencing of cDNAs encoding for the ubiquitously expressed PTX-sensitive G protein subunits G alpha i2, G alpha i3, G beta 1, and G beta 2 from NT and HT cell lines yielded no evidence for mutations in these genes. Although the molecular mechanisms remain to be defined, these data support the concept of a selective enhancement of signal transduction via PTX-sensitive G proteins in essential hypertension.

Base Sequence↗
PubMed1996

Effect of progressive systemic sclerosis on antral myoelectrical activity and gastric emptying.

In patients with progressive systemic sclerosis (PSS) suffering from chronic dyspepsia the stomach may be affected by this disease. The objective of this study was to investigate both antral myoelectrical activity and gastric emptying in PSS patients. Electrogastrography (EGG) was performed in 17 PSS patients (16 female, one male, median age 58 years, range 32-74 years) with chronic dyspepsia. After an overnight fast during one hour in the fasting and one hour in the fed state after ingestion of a liquid-solid test meal (370 kcal; liquid phase labeled with 0.5 mCi 99mTc-colloid) antral electrical activity was measured by one pair of electrodes sonographically placed on the skin overlying the gastric antrum. Several EGG parameters including dominant frequency (DF), percentages of DF in the normal range (2-4 cycles per minute [cpm]), bradygastria (< 2 cpm) and tachygastria (4-10 cpm), dominant frequency instability coefficient (DFIC), and postprandial to preprandial power ratio (PR) were calculated. The data were correlated to results obtained in 20 age- and gender-matched healthy subjects. In addition, the data were compared to gastric retention of the radionuclide at 60 min measured by simultaneous scintigraphy. The PSS patients did not reveal electrical disturbances. They even exhibited a significant postprandial decrease in DFIC, bradygastria, and tachygastria (ns) compared to healthy subjects. Over 50% of the PSS patients showed a delayed gastric emptying. However, EGG did not correlate to radioscintigraphy significantly. Our results reflect an absent relationship between antral myoelectrical activity in EGG and gastric emptying. Therefore, electrogastrography is unsuitable to assess gastric involvement in PSS.

Adult↗
PubMed1995

G protein regulation of the Na+/H+ antiporter in Xenopus laevis oocytes. Involvement of protein kinases A and C.

We have characterized the regulation of the endogenous Na+/H+ exchanger in Xenopus laevis oocytes by G proteins and protein kinases by measuring the ethylisopropylamiloride-sensitive Li+ uptake. Injection of oocytes with the stable GTP analog GTP gamma S stimulated Li+ uptake up to almost 4-fold, an effect blocked by coinjection with the GDP analog, guanyl-5'-yl thiophosphate. Injection into oocytes of beta gamma subunits of the heterotrimeric G protein transducin enhanced Li+ uptake by about 3-fold. This stimulation was blocked by transducin alpha subunits, which by themselves did not influence Li+ uptake. Using various activators and inhibitors of protein kinases, it is demonstrated that the X. laevis oocyte Na+/H+ antiporter can be stimulated by activation of both protein kinase A and C. Stimulation of Na+/H+ exchanger activity by GTP gamma S but not that induced by transducin beta gamma subunits was blocked by the protein kinase A inhibitor H-89. On the other hand, transducin beta gamma subunit-stimulated activity was prevented by the protein kinase C inhibitor, calphostin C. The non-selective protein kinase inhibitor H-7 blocked both GTP gamma S- and transducin beta gamma subunit-stimulated Na+/H+ exchanger activity. The results suggest that the Na+/H+ exchanger of X. laevis oocytes can be activated by G proteins and that this activation is not direct but mediated by protein kinase A- and/or protein kinase C-dependent pathways.

Animals↗
PubMed1995

Expression of the human sodium/proton exchanger NHE-1 in Xenopus laevis oocytes enhances sodium/proton exchange activity and establishes sodium/lithium countertransport.

We investigated whether the human sodium/proton (Na+/H+) exchanger isoform 1 (NHE-1) can mediate sodium/lithium (Na+/Li+) countertransport. Using the Xenopus laevis oocyte expression system we determined amiloride-sensitive Li+ uptake, a measure of Na+/H+ exchange, in oocytes injected with water or NHE-1 cRNA. Amiloride-sensitive Li+ uptake was three- to tenfold enhanced over control in NHE-1 cRNA-injected cells and was selectively inhibited by 0.01 microM HOE 694 [i.e. (3-methylsulphonyl-4-piperidinobenzoyl) guanidine methanesulphonate]. The endogenously present Na+/H+ exchanger was insensitive to HOE 694. After acidification of oocytes from pH 7.7 to 6.8, amiloride-sensitive Li+ uptake was four- to tenfold higher in NHE-1 cRNA-injected cells than in controls. Li+ efflux from control oocytes was independent of extracellular Na+, indicating that these cells expressed no measurable Na+/Li+ countertransport activity. In NHE-1 cRNA-injected oocytes, Li+ efflux was distinctly enhanced by extracellular Na+ ions. This Na(+)-dependent Li+ efflux was inhibited by ethylisopropylamiloride, phloretin and by cytosolic acidification. The data show that expression of the NHE-1 in X. laevis oocytes induces the expression of Na+/Li+ countertransport. The data confirm that Na+/H+ exchange and Na+/Li+ countertransport are mediated by the same transport system.

Amiloride↗
PubMed1994

Mechanisms of intraocular photodisruption with picosecond and nanosecond laser pulses.

Nd:YAG laser photodisruption with nanosecond (ns) pulses is an established method for intraocular surgery. In order to assess whether an increased precision can be achieved by the use of picosecond (ps) pulses, the plasma size, the shock wave characteristics, and the cavitation bubble expansion after optical breakdown with ps- and ns-laser pulses were investigated by time-resolved photography and acoustic measurements. Nd:YAG laser pulses with a duration of 30 ps and 6 ns, respectively, were focused into a water-filled glass cuvette. Frequency doubled light from the same laser pulses was optically delayed between 2 ns and 136 ns and used as illumination light source for photography. Since the individual events were well reproducible, the shock wave and bubble wall position could be determined as a function of time. From the slope of these r(t) curves, the shock wave and bubble wall velocities were determined, and the shock wave pressure was calculated from the shock velocity. The plasma size at various laser pulse energies was measured from photographs of the plasma radiation. The breakdown thresholds at 30 ps and 6 ns pulse duration were found to be 15 microJ and 200 microJ, respectively. At threshold, ps-plasmas are shorter than ns-plasmas, but at the same pulse energy they are always approximately 2.5 times longer. The initial shock pressures were 17 kbar after ps-pulses with an energy of 50 microJ, and 21 kbar after 1 mJ ns-pulses. The pressure amplitude decayed much faster after the ps-pulses. The maximum expansion velocity of the cavitation bubble was 350 m/s after a 50 microJ ps-pulse, but 1,600 m/s after a 1 mJ ns-pulse. The side effects of intraocular microsurgery associated with shock wave emission and cavitation bubble expansion can be considerably reduced by the use of ps-pulses, and new applications of photodisruption may become possible.

Eye↗
PubMed1994

[Schimmelpenning-Feuerstein-Mims syndrome (SFM syndrome)].

We report on the case of a 70-year-old caucasian woman with a large linear sebaceous naevus with multifocal intralesional basaliomas and a lipodermoid of the left eye. This rare finding has been preserved because of the special history of the patient. The naevus spread on the left side from parietal to retroauricular, nuchal and sternal. Because of the patient's cardio-pulmonary insufficiency we excised the basaliomas under local anaesthesia. We also made a partial stripped excision of the left-sided parietal parts of the naevus.

Aged↗
PubMed1994

The roles of uridine-cytidine kinase and CTP synthetase in the synthesis of CTP in malignant human T-lymphocytic cells.

The pattern of incorporation of [14C]uridine showed that in MOLT-3 cells an increased proportion of CTP was synthesized via CTP synthetase, compared to proliferating normal human T lymphocytes at a physiological concentration of cytidine (< 0.5 microM). Furthermore, in the proliferating normal human T lymphocytes similar patterns of incorporation of [14C]uridine were observed in the presence of the physiological concentration of cytidine and after addition of 2 microM of cytidine. In contrast, in the MOLT-3 cells after addition of 2 microM of cytidine the proportion of CTP synthesized by conversion of UTP into CTP was substantially decreased, whereas the salvage of cytidine was proportionally increased. We conclude that the reutilization of uridine is a preferred route in the synthesis of CTP for MOLT-3 cells at physiological concentrations of uridine and cytidine, whereas in proliferating normal human T lymphocytes CTP is largely synthesized through reutilization of cytidine. This difference in salvage of pyrimidine ribonucleosides may be exploited for selective chemotherapy.

Carbon Radioisotopes↗
PubMed1993

Evidence for transformation-related increase in CTP synthetase activity in situ in human lymphoblastic leukemia.

To determine the role of the enzyme CTP synthetase (EC 6.3.4.2) in the synthesis in situ of CTP in normal and in malignant lymphoblastic cells, the metabolism of radiolabeled pyrimidine ribonucleosides was studied in proliferating normal T lymphocytes and was compared with that of proliferating MOLT-3 cell-line cells and differentiated (non-proliferating) MOLT-3 cells. Both the incorporation of [14C]uridine into UTP and CTP and the incorporation of [14C]cytidine in CTP, as well as the fluxes of these labeled nucleosides through the nucleotide pools into nucleic acids, were elevated in proliferating MOLT-3 cells compared to proliferating T lymphocytes. Furthermore, the conversion of UTP into CTP was enhanced in proliferating MOLT-3 cells compared to proliferating T lymphocytes, indicating a higher activity of CTP synthetase in the leukemic cells. In non-proliferating MOLT-3 cells, the pyrimidine ribonucleotide fluxes were decreased compared to proliferating MOLT-3 cells and proliferating T lymphocytes. However, the decreased ratio of uracil/cytosine ribonucleotides that was found in proliferating T lymphocytes and proliferating MOLT-3 cells compared to non-proliferating blood lymphocytes, was preserved in the differentiated MOLT-3 cells. Moreover, although the fluxes had decreased, most CTP was still synthesized by CTP synthetase in the differentiated MOLT-3 cells. Thus, the elevated activity of CTP synthetase in MOLT-3 cells was independent of the cell growth and maturation stage. We conclude that the increased activity of CTP synthetase is associated with the process of malignant transformation in MOLT-3 cells. Therefore, CTP synthetase offers an attractive target for selective therapy in human acute T-lymphoid leukemia.

Carbon-Nitrogen Ligases↗
PubMed1993

Estimating glucose absorption in peritoneal dialysis using peritoneal equilibration tests.

To determine peritoneal dialysis patients' dietary energy requirements, the glucose absorbed from the dialysate needs to be quantified. The currently accepted method of estimating glucose absorption is based on the average glucose absorption of 7 continuous ambulatory peritoneal dialysis (CAPD) patients (Grodstein, 1981). Peritoneal equilibration test curves have shown that modality and transport characteristics affect glucose absorption. To test a more accurate procedure for estimating glucose absorption, we compared two different methods of determining the actual glucose absorption: Grodstein formula: (11.3 xa-10.9) liters of dialysate, where xa is the average glucose concentration, and the D/D0 formula: (1-D/D0)xi, where xi is the initial glucose instilled, using 4-hour D/D0 for CAPD and dwell time D/D0 for automated peritoneal dialysis (APD). Twenty-four-hour glucose absorption was measured in 50 CAPD patients and 17 APD patients. Absorption was calculated from the glucose remaining in the 24-hour spent dialysate. Wilcoxon sign rank statistical analysis showed the D/D0 formula results to be closer to actual glucose absorbed (CAPD: p = 0.0153; APD: p = 0.0001). The D/D0 formula is individualized for patients' modality and membrane characteristics and easy to calculate from readily available information.

Absorption↗
PubMed1993

The 24-hour D/P ratio is a convenient screen for identifying altered peritoneal transport rates.

Peritoneal transport characteristics (PTC) may change without peritonitis, surgery, or other insults. Identifying patients with these changes is essential in adjusting the dialysis prescription to achieve optimal peritoneal dialysis on a long-term basis. Frequent standard peritoneal equilibration tests (PETs) become impractical as the population in individual programs expands. The time demands are burdensome to the nursing staff as well as to the patient. The accuracy of fast PETs is dependent upon the patient's exact adherence to the protocol steps. Utilizing the 24-hour D/P as a marker for altered PTCs has improved the efficiency of our approach to repeating standard PETs and ensuring dialysis adequacy. For adequacy studies, pooled 24-hour dialysate is routinely collected in our unit. The 24-hour D/P ratio correlates well with extrapolations from original PET data and the patient's current dwell times. Discrepancies noted between the patient's actual D/P ratio and the patient's expected D/P ratio alert the clinician to possible PTC changes.

Biological Transport↗