The “Bantu Clinic”: A Genealogy of the African Patient as Object and Effect of South African Clinical Medicine, 1930–1990

This paper is about power, medicine andthe identity of the African as a patient of westernmedicine. From a conventional perspective and asencoded in the current quest for wholeness thatcharacterises South African biomedical discourse, theAfrican patient – like any other patient – has alwaysexisted as an authentic and subjectified being, whosetrue attributes and experiences have been denied bythe mechanistic, reductionistic and ethnocentricpractices of clinical medicine. Against this liberalhumanist perspective on the body as ontologicallyindependent of power, this paper offers a Foucaultianreading of the African patient as – like any otherpatient – contingent upon the force relations immanentwithin and relayed through the clinical practices ofbiomedicine. A quintessential form of disciplinarymicro-power, these fabricate the most intimaterecesses of the human body as manageable objects ofmedical knowledge and social consciousness to makepossible the great control strategies of repression,segmentation and liberation that are the usual focusof conventional investigations into the place andfunction of medicine in society. Since the 1930s whenthe African body first emerged as a discrete object ofa secular clinical knowledge, these have repeatedlytransformed the attributes and identity of the Africanpatient, and the paper traces this archaeology ofSouth African clinical perception from then until the1990s to show how its quest for wholeness is not anend point of discovery or liberation, but merelyanother ephemeral crystallization of socio-medicalknowledge in a constantly changing force field ofdisciplinary power.     

The identification of a DNA polymorphism of the α fibrinogen gene,and the regional assignment of the human fibrinogen genes to 4q26-qter

Summary We have identified a common restriction fragment length polymorphism of the fibrinogen gene with the enzyme TaqI. This polymorphism is probably due to a single base change that creates or destroys a TaqI recognition site about 1000 basepairs from the 3 end of the fibrinogen géne. The frequency of the rare allele in 83 unrelated healthy individuals is 0.33. We have used in situ hybridisation of the fibrinogen cDNA to localise the gene on chromosome 4q29–31. We have confirmed this regional localisation by restriction fragment detection in a human x Chinese hamster somatic cell hybrid which contains a translocated human chromosome 4 with a breakpoint at 4q26. The , , and fibrinogen genes are all present on human chromosome 4q26-qter.     

Alpha-1 and alpha-2 adrenoceptor binding in cerebral cortex: Role of disulfide and sulfhydryl groups

The triated adrenergic antagonists Prazosin ([³H]PRZ) and Idazoxan ([³H]IDA, or RX-781094) bind specifically and with high affinity to ₁ and ₂-adrenoceptors respectively, in membrane preparations from cerebral cortex. Saturation experiments performed to determine the density of receptors and the dissociation constant (K _d) were analyzed by the methods of Eadie Hofstee, iterative modelling, and the procedure of Hill, while the specificity of the labelling was verified by displacement experiments. Since receptors are proteins, we examined the role of disulfide (–SS–) bridges and sulfhydryl (–SH) groups in the specific combination of [³H]PRZ and [³H]IDA to the ₁ and ₂-adrenoceptors. Pretreatment of the membranes with the –SS– reactive DL-dithiothreitol (DTT) or the alkylating agent N-ethylmaleimide (NEM), alone or in combination, decreased specific binding of both ligands, with only minor changes in the non-specific counts. The [³H]IDA binding (₂-sites) was more sensitive to both DTT and NEM than the [³H]PRZ sites (₂-adrenoceptors), and the initial changes induced by alkylation of the ₂-site were due to an important decrease in the affinity for [³H]IDA, as judged by the increase in theK _d. This modulation in the affinity caused by alkylation of a thiol group could explain the higher potency of the blocking agent tetramine disulfide benextramine at the ₂-site. The results provide evidence for the participation of –SS– and –SH groups in the binding site of ₁ and ₂-adrenoceptors in the cerebral cortex.     

Ascorbic acid transport in mouse and rat astrocytes is reversibly inhibited by furosemide,SITS, and DIDS

The uptake ofL-ascorbic acid (vitamin C) by astrocytes was studied using primary cultures prepared from the neopallium of newborn Swiss CD-1 mice or Sprague-Dawley rats. Initial uptake rates were significantly greater in mouse than in rat astrocytes. Exposure of cultures to 0.25 mM dibutyryl cyclic AMP for 2 weeks changed cell morphology from polygonal to stellate and stimulated ascorbate uptake, with the greatest stimulation occurring in mouse astrocytes. Uptake was specific for the vitamin since it was not diminished by the presence of other organic anions including acetate, formate, lactate, malonate, oxalate, p-aminohippurate, pyruvate and succinate. Ascorbate uptake was Na⁺-dependent but did not have a specific requirement for external Cl^– (Cl^– ₀). Substitution of Cl^– ₀ by Br^– or NO₃ ^– decreased ascorbate uptake rates by 20–31%; whereas substitution by gluconate or isethionate increased uptake by 20–31%. Ascorbate transport by astroglial cultures from both animal species was rapidly (1 min) and reversibly inhibited by the anion transport inhibitors furosemide, 4-acetamido-4-isothiocyanostilbene-2,2-disulfonic acid (SITS) and 4,4-diisothiocyanostilbene-2,2-disulfonic acid (DIDS). The rapid and reversible effects of the impermeant inhibitors (SITS and DIDS) are consistent with direct inhibition of ascorbate transporters located in the astroglial plasma membrane.     

Measurement of three-bond coupling constants in the osmoregulated periplasmic glucan of Burkholderia solanacearum

Summary The cyclic osmoregulated periplasmic glucan produced by Burkholderia solanacearum contains 13 glucose units, all -(1–2) linked except for one -(1–6) linkage. We report here the measurement of the ³J(C1-H2) and ³J(H1-C2) coupling constants, characterizing the glycosidic linkages, through the use of a ¹³C/¹²C double half-filtered NOESY experiment. The values obtained give information about the (, ) angles of the different linkages. The results presented form an important step towards a detailed experimental model of the cyclic glucan, which might allow us to clarify its biological role and establish whether the cavity of these molecules is compatible with the capability of complexing host molecular signals.     

Angular dependence of 1J(Ni,Calphai) and 2J(Ni,Calpha(i-1)) coupling constants measured in J-modulated HSQCs

A new method to measure ¹J(N_i,C _i) and ²J(N_i,C _{(i – 1)}) coupling constants in proteins based on a J-modulated sensitivity enhanced HSQC was introduced. Coupling constants were measured in the denatured and in the native state of ubiquitin and found to depend on the conformation of the protein backbone. Using a combined data set of experimental coupling constants from ubiquitin and staphylococcal nuclease (Delaglio et al., 1991), the angular dependence of the coupling constants on the backbone angles and was investigated. It was found that the size of ²J(N_i,C _{(i – 1)}) correlates strongly with the backbone conformation, while only a weak conformational dependence on the size of ¹J(N_i,C _i) coupling constants was observed. Coupling constants in the denatured state of ubiquitin were uniform along the sequence of the protein and not dependent on a given residue type. Furthermore it was shown that the observed coupling constants were in good agreement with predicted coupling constants using a simple model for the random coil.     

Ca2+ oscillation in the homogenate ofPhysarum plasmodium

Summary Using aequorin luminescence, we observed a distinct oscillation in Ca²⁺ levels in the supernatant of the homogenate ofPhysarum plasmodium. Ca²⁺ oscillation continued for 10–120 minutes, with a period coinciding with that of the contraction rhythm of a plasmodium.Abbreviations EDTA Ethylenediaminetetraacetic acid - EGTA Ethyleneglycol-bis-(-aminoethylether)-N,N-tetraacetic acid - PIPES Piperazine-N,N-bis-(2-ethane sulfonic acid) - DTT Dithiothreitol The present work was supported by Grants-in Aid from the Ministry of Education, Science and Culture, Japan.     

Reduced sensitivity of Niemann-Pick C1-deficient cells to θ-toxin (perfringolysin O): sequestration of toxin to raft-enriched membrane vesicles

-Toxin (perfringolysin O) binds to cell surface cholesterol and forms oligomeric pores that cause membrane damage. Both in cytotoxicity and cell survival assays, a mutant Chinese hamster ovary cell line NPC1(–) that lacked Niemann-Pick C1 showed reduced sensitivity to -toxin, compared with wild-type (wt) cells. BC is a derivative of -toxin that retains cholesterol-binding activity but lacks cytotoxicity. Confocal and electron microscopy revealed the presence of multiple vesicles which bound BC, both on the cell surface and in the extracellular space of these cells. BC binding to raft microdomains was verified by its resistance to 1% Triton X-100 at 4°C and recovery of bound BC in floating low-density fractions on sucrose density gradient fractionation. BC-labeled vesicles were abolished when NPC1(–) cells were depleted of lipoproteins and also when treated with a Rho-associated kinase inhibitor Y-27632. In addition, similar vesicles were observed in wt cells treated with progesterone. In parallel with these results, -toxin sensitivity of NPC1(–) cells was increased when cells were depleted of lipoproteins or treated with Y-27632, whereas that of wt cells was decreased by progesterone. Our findings suggest that sequestration of toxin to raft-enriched cell surface vesicles may underlie reduced sensitivity of NPC1-deficient cells to -toxin.     

Acyl chain conformational ordering in liquid-crystalline bilayers: comparative FT-IR and 2H-NMR studies of phospholipids differing in headgroup structure and chain length

FT-IR spectroscopy has been used to evaluate the acyl chain conformational ordering of DMPC, DMPE, DMPA (pH 6 and 12), DMPG (pH 1 and 7), and DPPC, DPPE, DPPA (pH 6). The frequencies of the symmetric and antisymmetric methylene stretching vibrations were determined as a function of temperature. In the liquid-crystalline phase the frequencies show a qualitative dependence on the amount of chain disorder. Quantitative data for trans-gauche isomerization were obtained from the integral intensities of the conformation sensitive methylene wagging absorptions at ca. 1368 cm^–1 (gtg and gtg sequences), 1356 cm ^–1 (double gauche) and 1342 cm^–1 (end gauche). The integral band intensities were converted to the number of gauche conformers per acyl chain using the calibration factors published by Senak et al. (1991). At 69°C the highest number of gauche conformers excluding contributions from single gauche conformers and jogs (gtttg) are found for PCs (DMPC: 2.6; DPPC: 2.4), followed by DMPG^– (2.0), phosphatidylethanolamines (DMPE: 1.4; DPPE: 2.0), protonated DMPG (1.5), and phosphatidic acids (DPPA^–: 1.7; DMPA^–: 1.4, DMPA^2–: 1.7). From ²H-NMR measurements of perdeuterated samples of DMPC, DMPA, DPPC, and DPPA the quadrupolar splittings _Qi and the order parameter S _CDi of the CD₂-segments close to the chain ends could be determined whereas splittings in the plateau region of the chains could not be resolved. The quadrupolar splittings are affected by trans-gauche isomerization, long axis rotation, and restricted wobbling motions of the acyl chains. In the simplest assumption, the order parameter S_CD can be expressed as a product of a segmental order parameter S and a lhain order parameter S . For comparison of the different lipids we used average order parameters S_CD, obtained by averaging over all values, and S determined from the total number of gauche conformers per chain by FT-IR-spectroscopy, to calculate an empirical average chain order parameter S. The combination of ²H-NMR and FT-IR results allows the estimation of the relative extent of chain wobbling for the different lipid molecules. S is lowest for PCs (S 0.475) while PEs (S 0.51) and PAs (S0.52) show less chain wobbling.Abbreviations FT-IR Fourier transform infrared - ²H-NMR deuterium nuclear magnetic resonance - DMPC(–d₅₄) (perdeuterated) dimyristoyl-phosphatidylcholine - DMPE(–d₅₄) (perdeuterated) dimyristoyl-phosphatidylethanolamine - DMPA(–d₅₄) (perdeuterated) dimyristoyl-phosphatidic acid - DMPG dimyristoyl-phosphatidylglycerol - DPPC(–d₆₂) (perdeuterated) dipalmitoyl-phosphatidylcholine - DPPE(–d₆₂) (perdeuterated) dipalmitoyl-phosphatidylethanolamine - DPPA(–d₆₂) (perdeuterated) dipalmitoyl-phosphatidic acid - gtg gauche ^±-trans-gauche^± - gtg gauche^±-trans-gauche^± - dg double gauche - eg end gauche Correspondence to: A. Blume     

Internalization of glial cell-derived neurotrophic factor receptor GFR alpha 1 in the absence of the ret tyrosine kinase coreceptor

1. Glial cell-derived neurothrophic factor (GDNF) interacts with a cell surface receptor, GFR1, that is linked via a glycosyl-phosphatidylinositol (GPI) lipid to the cell membrane. The neurotrophic activities of GDNF are mediated by binding to GFR1 and further interaction of the GDN–GFR1 complex with a coreceptor tyrosine kinase encoded by the c-Ret protooncogene. There is also evidence for the existence of cell signaling by GDNF and GFR1 in the absence of Ret.2. To further delineate the Ret-dependent and -independent functions of GDNF, cellular internalization of GDNF and GFR1 was examined in cells lines and primary neurons.3. Relative to other GPI-anchored receptors, efficient endocytosis ( 30–40% of total surface-bound ligand internalized after 2 min) of GNDF and GFR1 was observed in neuroblastoma and transfected-fibroblast cell lines that lack Ret. Primary hippocampal neurons from transgenic mice that express a wild-type GFR1 together with a mutant, tyrosine kinase-inactive Ret also internalized GDNF efficiently ( 20% of total surface-bound ligand internalized after 2 min). We also observed a ligand dependence for GFR1 internalization in the cell lines that lack Ret. Furthermore, a comparison in the presence and absence of Ret indicates that this coreceptor tyrosine kinase slows internalization at early time points.4. The data suggest different mechanisms of internalization for GDNF–GFR1 in the absence and presence of the Ret coreceptor.     

Carotenoid pigments of Sorangium compositum (Myxobacterales) including two new carotenoid glucoside esters and two new carotenoid rhamnosides

Summary The carotenoid pigments of the myxobacterium Sorangium compositum were analyzed by chromatographical and chemical techniques and by visible, infra red, and mass spectroscopy. Besides -carotene, neurosporene, torulene, lycopene, and 1,2-dihydro-1-hydroxy--carotene, four new carotenoid glycosides were found. These pigments were identified as 1,2-dihydro-1-hydroxy-torulene glucoside ester (I), 1,2-dihydro-3,1-dihydroxy-torulene glucoside ester (III), 1,2-dihydro-1-hydroxy-torulene rhamnoside (II), and 1,2-dihydro-3,1-dihydroxytorulene rhamnoside (IV).Fifth communication on the carotenoids of myxobacteria. Fourth communication see Arch. Mikrobiol. 76, 364–380 (1971).     

Effects of α-bungarotoxin on acetylcholine-induced response at the Helix neuronal membrane

The effects of -bungarotoxin (-BT) on two patterns of acetylcholine (ACh)-induced response differing in desensitization rate were investigated in isolated mollusk neurons using intracellular dialysis and concentration clamping techniques. It was found that -BT depressed both types of ACh-induced response — a reversible action in the majority of experiments performed. It also exerted a blocking effect on ACh-induced currents dependent on the presence of albumin, although albumin itself produced no noticeable change in ACh-induced response. Concentration dependence of -BT-induced blockade on both types of currents evoked by 1 and 10 µM ACh was investigated. The -BT concentrations producing a 50% suppression of the current evoked by 1 µM ACh were calculated by approximating concentration plots as (13.85±1.25)×10^–9 and (5.56±1.0)×10^–8 g/ml for type A and B cells respectively.Institute of Experimental Biology. Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 21, No. 6, pp. 729–735, November–December, 1989.     

Identification of a glutathione-S-transferase effector domain for inhibition of jun kinase, by molecular dynamics

We have recently found that the glutathione-S-transferase -isozyme (GST-), a cellular detoxification enzyme, potently and selectively inhibits activation of jun protein by its upstream kinase, jun kinase (JNK). This newly identified regulatory activity of GST- is strongly inhibited by a group of agents that inhibit its enzymatic activity. Since loss of enzymatic activity in general does not correlate with loss of regulatory activity, it is likely that inhibitor binding induces changes in the structure of one or more domains of GST that block its interaction with JNK. To identify regions of GST that change conformation on the binding of inhibitors, we have performed molecular dynamics calculations on GST- to compute its average structure in the presence and absence of the inhibitor, glutathione sulfonate. Superposition of the two average structures reveals that several regions change local structure depending upon whether the inhibitor is bound or not bound. Two of these regions, residues 36–50 and 194–201, are highly exposed. We have synthesized peptides corresponding to these two segments and find that the 194–201 sequence strongly inhibits the ability of GST- to block the in vitro phosphorylation of jun by JNK. These results suggest that this region of GST- is critical to its functioning as a newly discovered regulator of signal transduction.     

Use of15N/14N rations to evaluate the food source of the mysid,Neomysis intermedia Czerniawsky,in a eutrophic lake in Japan

The stable isotope ratios of nitrogen were measured in the mysid,Neomysis intermedia, together with various biogenic materials in a eutrophic lake, Lake Kasumigaura, in Japan throughout a year of 1984/85. The mysid, particulate organic matter (POM, mostly phytoplankton), and zooplankton showed a clear seasonal change in ¹⁵N with high values in spring and fall, but the surface bottom mud did not. A year to year variation as well as seasonal change in ¹⁵N was found in the mysid. The annual averages of ¹⁵N of each material collected in 1984/85 are as follows: surface bottom mud, 6.3 (range: 5.7–6.9); POM, 7.9 (5.8–11.8); large sized mysid, 11.6 (7.7–14.3); zooplankton, 12.5 (10.0–16.4); prawn, 13.2 (9.9–15.4); goby, 15.1 (13.8–16.7). The degree of¹⁵N enrichment by the mysid was determined as 3.2 by the laboratory rearing experiments. The apparent parallel relationship between the POM and the mysid in the temporal patterns of ¹⁵N with about 3 difference suggests the POM (mostly phytoplankton) as a possible food source ofN. intermedia in this lake through the year.     

Diazoxide and Pinacidil Uncouple Pyruvate–Malate-Induced Mitochondrial Respiration

We investigated the effects of K_ATP channel openers diazoxide and pinacidil on the respiration rate and membrane potential () of rat heart mitochondria, oxidizing pyruvate and malate. Diazoxide and pinacidil (58.8–1348.3 M) increased the V ₂ (-ADP) respiration rate accordingly by 13–208% and 30–273% and decreased the by 2–17% and 6–55%. These effects were also similar in the respiration medium without K⁺. Moreover, carboxyatractyloside completely abolished diazoxide- and pinacidil-induced uncoupling, indicating a role for the mitochondrial adenine nucleotide translocase in this process.     

Use of 4-Thiouridine and 4-Thiothymidine in Studies on Pyrimidine Nucleoside Phosphorylases

The new substrates 4-thiouridine and 4-thiothymidine were proposed for spectrophotometric measurement of the activity of uridine (UP) and thymidine (TP) phosphorylases. At pH 7.5, 4-thiouridine has an absorbance maximum at 330 nm, and the difference in extinction coefficient () between 4-thiouridine and 4-thiouracil is 3000 ^–1cm^–1. 4-Thiouridine proved to be a good substrate for UP: the Michaelis ( ) and catalytic (k _cat) constants were estimated respectively at 130 M and 49 s^–1 at 25°C. Even a greater (5000 M^–1cm^–1 at 336 nm) was observed for the 4-thiothymidine/4-thiothymine pair.     

Water uptake and transport in lianas and co-occurring trees of a seasonally dry tropical forest

Water uptake and transport were studied in eight liana species in a seasonally dry tropical forest on Barro Colorado Island, Panama. Stable hydrogen isotope composition (D) of xylem and soil water, soil volumetric water content (_v), and basal sap flow were measured during the 1997 and 1998 dry seasons. Sap flow of several neighboring trees was measured to assess differences between lianas and trees in magnitudes and patterns of daily sap flow. Little seasonal change in _v was observed at 90–120 cm depth in both years. Mean soil water D during the dry season was –19 at 0–30 cm, –34 at 30–60 cm, and –50 at 90–120 cm. Average values of xylem D among the liana species ranged from –28 to –44 during the middle of the dry season, suggesting that water uptake was restricted to intermediate soil layers (30–60 cm). By the end of the dry season, all species exhibited more negative xylem D values (–41 to –62), suggesting that they shifted to deeper water sources. Maximum sap flux density in co-occurring lianas and trees were comparable at similar stem diameter (DBH). Furthermore, lianas and trees conformed to the same linear relationship between daily sap flow and DBH. Our observations that lianas tap shallow sources of soil water at the beginning of the dry season and that sap flow is similar in lianas and trees of equivalent stem diameter do not support the common assumptions that lianas rely primarily on deep soil water and that they have higher rates of sap flow than co-occurring trees of similar stem size.     

Life tables of Moina macrocopa (Straus) in successive generations under food and temperature adaptation

Life tables of Moina macrocopa (Straus) cultured at seven foodconcentrations (FC) (Scenedesmus sp., 1.49–1490 mg wet weightl^-1, 10⁴–10⁶ cellml^-1) were investigated for animals of the first generation(nonadapted animals) and for animals of the third generation (adaptedanimals) cultivated at these FC. Adapted animals showed a trophicpreferendum, i.e. a narrow FC-range at which maximal R_ovalues were observed in comparison with nonadapted animals. In adaptedanimals, the maximal R_o was 115.3 individual, observed at 20°C and a FC of 74.5 mg wet weight l^-1.     

Enteromorpha as a monitor of heavy metals in estuaries

An account is given of the use of Enteromorpha to monitor zinc, cadmium, mercury and lead pollution in six estuaries and the British North Sea coast. The ranges for each element were: Zn, 19–437 µg g^–1; µg g^–1 Cd, 0.07–4.8 µg g^–1; Hg, 0.02–0.23 µg g^–1. It is suggested that tissue analysis of Enteromorpha is one of the most useful biological techniques available in estuaries for pin-pointing aqueous (as opposed to sediment) metal contamination, and also for providing data suitable for world-wide comparisons. Provisional values are given for concentrations corresponding to moderate and high pollution.Deceased     

Studies of the mechanisms of toxicity of the administration of recombinant tumor necrosis factor α in normal and tumor-bearing mice

Summary Tumor-bearing mice have a greater sensitivity to the acute lethal effects of the administration of high-dose recombinant human tumor necrosis factor (rhTNF-) compared to normal, non-tumor-bearing mice. We studied whether or not the presence of tumor per se was responsible for the enhanced rhTNF- toxicity. Tumor-bearing mice underwent tumor excision or sham operation before the systemic administration of rhTNF at staged times (0.5–24 h) following surgery. There was little survival difference between sham-operated tumor-bearing mice and tumor-bearing mice undergoing tumor excision (at 24 h, treatment with 12 µg rhTNF-, survival:sham-operated tumor bearers = 0/12, excised tumor-bearers = 0/12;P ² <0.01 compared to non-tumor-bearers). Mice without tumors receiving sham operation, had minimal toxicity (10 of 12 mice surviving). The injection of 3 ml Ringer's lactate i.p. before i.v. rhTNF- therapy increased survival in tumor-bearing animals; following pretreatment with Ringer's lactate 30/42 mice survived 12 µg rhTNF- compared to 6/42 surviving a similar rhTNF- dose without hydration (P ² <0.001). Since the production of oxygen free-radical metabolites has been postulated to play a role in the acute toxicity of rhTNF-, bismuth subnitrate was used to induce the enzyme metallothionein to act as a natural scavenger for these metabolites. Daily oral bismuth subnitrate treatments improved survival of mice with MCA-106 or MCA-102 sarcoma and of mice without tumors, with higher rhTNF- doses (12–20 µg), without reducing the therapeutic effect of rhTNF- against the weakly immunogenic MCA-106 sarcoma. These studies suggest methods for reducing the toxicity of rhTNF- administration in clinical trials.