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J Zanen

Publications and source records attributed to J Zanen.

At least 19 recordsLinked to original sources
PubMed1997

Attenuation of gentamicin-induced nephrotoxicity in rats by fleroxacin.

The effect of fleroxacin on gentamicin-induced nephrotoxicity was evaluated with female Sprague-Dawley rats. Animals were injected during 4 or 10 days with saline (NaCl; 0.9%), gentamicin alone at doses of 10 and 40 mg/kg of body weight/12 h (subcutaneously), fleroxacin alone at a dose of 25 mg/kg/12 h (intraperitoneally), or the combination gentamicin-fleroxacin in the same regimen. Gentamicin induced a dose- and time-dependent renal toxicity as evaluated by gentamicin cortical levels, sphingomyelinase activity in the renal cortex, histopathologic and morphometric analysis, blood urea nitrogen and serum creatinine levels, and cellular regeneration ([3H]thymidine incorporation into DNA of cortical cells). The extent of these changes was significantly reduced when gentamicin was given in combination with fleroxacin. Although the mechanisms by which fleroxacin reduces the nephrotoxic potential of gentamicin are unknown, we propose that the fleroxacin-gentamicin combination enhances exocytosis activity in proximal tubular cells, as suggested by the higher excretion of urinary enzymes and lower cortical levels of gentamicin observed in animals treated with the combination fleroxacin-gentamicin compared with those treated with gentamicin alone. The protective effect of fleroxacin on gentamicin nephrotoxicity should be investigated further.

Animals↗
PubMed1996

Involvement of transforming growth factor-alpha and its receptor in a model of DES-induced renal carcinogenesis in the Syrian hamster.

This study explores the role played by TGF alpha in estrogen-induced renal tumors. Tumors were induced in male Syrian hamster by chronic administration of diethylstilbestrol (DES). Six experimental groups (n = 5-9) were chronically exposed to DES and sacrificed after 1, 2, 4, 6, 9 and 11 months, respectively. In the course of treatment, the nephrons were the site of an important increase of cell turnover, which was characterized by a process of hyperplasia/dysplasia in proximal tubules preceding the neoplastic transformation. In treated animals and in controls, the analysis of renal tissue by Western blot revealed the presence of a 6 kDa polypeptide crossreacting with anti-TGF alpha antibody. In controls, TGF alpha immunoreactivity was localized in proximal and in distal tubules. Before tumor development (1-4 months), TGF alpha RIA showed an increase of TGF alpha concentration in renal tissue, in parallel with the increased cell proliferation observed in proximal tubules. In addition, Western blot analysis also demonstrated in kidney tissue the presence of a 165 kDa protein displaying the immunoreactivity of EGF/TGF alpha receptor. The receptor immunoreactivity was localized in proximal tubular cells suggesting an involvement of TGF alpha in tubular epithelial growth through autocrine or paracrine pathways. In large neoplasms, immunocytochemistry revealed only clusters of transformed cells intensely stained by the anti-TGF alpha antibody. These cells displayed the appearance of stellate or polyhedric cells infiltrating adjacent neoplastic tissues. Antisera raised against intra- or extracytoplasmic domains of the EGF/TGF alpha receptor were assayed to localize this receptor in the tumors. In contrast with tubular structures, immunoreactivity to EGF/TGF alpha receptor was never detected in tumoral tissue. The apparent absence of EGF/ TGF alpha receptor immunoreactivity in malignant cells seems to exclude an involvement of this growth factor in the tumorigenic process, although it could be involved in tumor neovascularization.

Amino Acid Sequence↗
PubMed1996

In situ demonstration of germinal cell apoptosis during diethylstilbestrol-induced testis regression in adult male Syrian hamsters.

Testis regression was induced in male Syrian hamsters by chronic exposure to diethylstilbestrol (DES), and estradiol-17 beta agonist. Experimental groups (n = 4-5) were killed at increasing time intervals over a period of 6 mo after initiation of treatment. Apoptosis in testes was demonstrated by in situ analysis of DNA fragmentation. Cell proliferation was monitored by immunostaining nuclei of S-phase cells after pulse labeling with 5-bromo-2'-deoxyuridine. Levels of FSH and testosterone, measured by RIA fell rapidly in DES-treated hamsters. In parallel, testis weight and seminiferous tubule area underwent an 80% decrease during the first 2 wk of DES administration. The composition of seminiferous epithelium was also drastically affected by DES, since it became progressively confined to Sertoli cells, spermatogonia, and spermatocytes. Testis regression was associated with an important increase of apoptosis, which started 3 days after the beginning of DES administration. Apoptosis was still 10- to 50-fold higher than in control testes by the end of treatment; it affected primarily spermatocytes and, to a much lesser extent, spermatogonia. Cell proliferation was not inhibited by chronic DES administration. In conclusion, these data indicate that apoptosis can by itself account for estrogen-induced testis regression.

Animals↗
PubMed1996

Pulmonary emphysema: quantitative CT during expiration.

PURPOSE: To determine whether measurement of the relative area of lung with attenuation coefficients lower than a certain threshold on thin-section computed tomographic (CT) scans obtained during expiration is a valuable method of quantifying the extent of pulmonary emphysema. MATERIALS AND METHODS: Eighty-nine patients underwent CT (with 1-mm collimation) preoperatively during inspiration and expiration. Relative areas of lung with attenuation coefficients lower than various thresholds were calculated. These relative areas were compared with areas found macroscopically to have emphysema (59 patients [51 men, eight women; aged 40-77 years]) and with two microscopic indices (35 patients [29 men, six women; aged 42-77 years]) assessed on the resected specimens. RESULTS: The valid expiratory CT thresholds were found to be -820 and 910 HU for microscopic and macroscopic emphysema, respectively. However, results of stepwise multiple regression analyses showed that the inspiratory threshold of -950 HU was superior for both macroscopically and microscopically quantified emphysema. The correlation coefficients in expiratory CT were higher for the pulmonary volumes but similar for the diffusing capacity. CONCLUSION: Expiratory quantitative CT is not as accurate as inspiratory CT for quantifying pulmonary emphysema and probably reflects air trapping more than reduction in the alveolar wall surface.

Adult↗
PubMed1996

Comparison of computed density and microscopic morphometry in pulmonary emphysema.

The purpose of this prospective study was to verify whether the percentage area of lung occupied by lowest attenuation values on high-resolution computed tomography (HRCT) scans reflects microscopic emphysema and to compare this quantification with the information yielded by the most widely used pulmonary function tests (PFT). Preoperative HRCT scans were obtained with 1-cm intervals in 38 subjects. With a semiautomatic evaluation procedure, the percentage areas occupied by attenuation values inferior to thresholds ranging from -900 Hounsfield units (HU) to -970 HU were calculated for the lobe or lung to be resected. Emphysema was microscopically quantified by using a computer-based method, measuring the perimeters and interwall distances of alveoli and alveolar ducts. The strongest correlation was found for -950 HU. As a second step, we evaluated possible correlations between PFT and microscopic measurements. Finally, considering the microscopic measurements as a standard, we tried to investigate their relationships with each of the PFT and with the relative area occupied by attenuation values lower than -950 HU for both lungs. This revealed that the diffusing capacity for carbon monoxide associated with HRCT quantification is sufficient to predict microscopic measurements. We concluded that the percentage area of lung occupied by attenuation values lower than -950 HU is a valid index of pulmonary emphysema.

Adult↗
PubMed1995

Macroscopic assessment of pulmonary emphysema by image analysis.

AIMS: To propose a computerised image analysis based method for measuring, on paper mounted lung sections, the area macroscopically occupied by emphysema. METHODS: The study was based on the assessment of 69 lung sections prepared following a modified Gough-Wentworth technique. The results obtained from image analysis, point counting, and panel grading methods were compared, as was the repeatability of image analysis and panel grading. RESULTS: The results from image analysis and from point counting were not significantly different (p = 0.609) and significant quadratic regressions (r = 0.96, p < 0.001) were found between measurements from image analysis and from panel grading, the computerised technique being shown to be the most reproducible. CONCLUSIONS: Image analysis is a valuable and reproducible method to measure the area of lung macroscopically involved by emphysema.

Histocytological Preparation Techniques↗
PubMed1995

Comparison of computed density and macroscopic morphometry in pulmonary emphysema.

High-resolution computed tomography (HRCT) scans were obtained at 1 cm intervals in 63 subjects referred for surgical resection of a cancer or for transplantation to find out whether the relative area of lung occupied by attenuation values lower than a threshold would be a measurement of macroscopic emphysema. Using a semiautomatic procedure, the relative areas occupied by attenuation values lower than eight thresholds ranging from -900 to -970 HU were calculated on the set of scans obtained through the lobe or the lung to be resected. The extent of emphysema was quantified by a computer-assisted method on horizontal paper-mounted lung sections obtained every 1 to 2 cm. The only level for which no statistically significant difference was found between the HRCT and the morphometric data was -950 HU. To determine the number of scans sufficient for an accurate quantification, we recalculated the relative area occupied by attenuation values lower than -950 HU on progressively fewer numbers of scans and investigated the departure from the results obtained with 1 cm intervals. Because of wide variations in this departure from patient to patient, a standard cannot be recommended as the optimal distance between scans.

Adult↗
PubMed1994

Potentiation of gentamicin nephrotoxicity in the rat by infusion of aprotinin.

The present study was undertaken to examine a possible effect of aprotinin, a 6.5-kDa polypeptide with an inhibitory effect on proteolysis, on aminoglycoside nephrotoxicity. Experimental animals (female Sprague-Dawley rats, 175-200 g body wt) were treated for 4 days with 40 mg/kg gentamicin given ip at 12-hr intervals. Aprotinin (40,000 kIU per animal) was infused i.v. over a period of 8 days, using subcutaneously implanted miniosmotic pumps. In protocol A, infusion pumps were placed 4 days before starting gentamicin treatment. In protocol B, pumps were implanted 15-18 hr prior to first gentamicin administration. In addition to rats exposed to both gentamicin and aprotinin (GAP), animals were treated with gentamicin ip+saline i.v. (G), saline ip+aprotinin i.v. (AP), or received only saline by both routes of administration (C). All rats were terminated 4 days after the end of gentamicin dosing. One hour before sacrifice, 200 microCi of [3H]thymidine was given ip to each animal in order to monitor cell turnover in renal tissue. The kidneys were analyzed with respect to (i) histopathological alterations and renal dysfunction, (ii) aminoglycoside tissue accumulation, and (iii) tubular regeneration (measurement of cell proliferation). In animals receiving aprotinin alone, histological examination of renal cortex on paraffin sections disclosed mild tubular injury with focal cell necrosis. In plastic-embedded tissue, proximal tubule epithelium was characterized by the presence of numerous inclusions densely stained with toluidine blue. At the ultrastructural level, these inclusions appeared filled with amorphous electron-dense material. In gentamicin-treated animals, cortical drug accumulation reached values higher than 0.3 mg/g renal tissue, but a significant 30-40% decrease of gentamicin accumulation was noted in GAP groups, compared to G groups. Histological examination of renal cortex (paraffin sections) revealed the development of acute tubular necrosis in both G and GAP groups. Tubular injury was accompanied by mild renal dysfunction, as shown by the level of serum creatinine which was increased almost 3-fold in the G group, compared to C and AP groups. Aprotinin infusion produced a further increase of serum creatinine, particularly in protocol A where it was 72% higher for the GAP group than for the G group. In both G and GAP groups, postnecrotic tubular regeneration was evidenced by determining the rate of DNA synthesis and the frequency of S-phase cells in renal cortex. Both methods gave consistent results and showed a 8- to 13-fold increase of cell proliferation in groups receiving gentamicin alone, compared to C groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Modification of immunoreactive EGF and EGF receptor after acute tubular necrosis induced by tobramycin or cisplatin.

Acute tubular necrosis induced by aminoglycoside antibiotics and various other nephrotoxins is followed by a regenerative process which leads to the restoration of damaged tubules. Several lines of evidence indicate that tubular regeneration is mediated by polypeptide growth factors such as epidermal growth factor (EGF). Previous studies devoted to cisplatin nephrotoxicity have shown that this agent causes tubular cystic degeneration possibly related to an impairment of renal tissue repair. Thus, we examined on a comparative basis the time course of the regenerative response subsequent to tubular damage induced by tobramycin or cisplatin, particular attention being paid to renal EGF and its receptor. Female Sprague-Dawley rats (160-180 g body weight) were treated during 4 consecutive days with daily doses of 200 mg/kg tobramycin i.p. (BID) or 2 mg/kg cisplatin (once a day). Sham-treated rats were given 0.9% NaCl i.p. following the same protocol. Groups of experimental animals (n = 5-10) were terminated at increasing time intervals (1, 4, 7, 14, 21, 60 days) after cessation of treatment. One hour prior to sacrifice, each individual received i.p. 200 mg/kg 5-bromo-2'-deoxyuridine (BrdU) for the immunohistochemical demonstration of cell proliferation. Blood was collected at the time of sacrifice in order to assess glomerular filtration rate by measuring serum creatinine and BUN levels. Kidneys were analyzed with respect to total EGF determined by RIA in renal tissue homogenates, and soluble EGF was assayed in extracts prepared by centrifugation. Renal tissue was processed for the immunohistochemical detection of S-phase cells, of EGF, of EGF receptors, and of the intermediate filament vimentin, the latter being used as a marker of epithelium dedifferentiation. In absence of nephrotoxic alterations, EGF was immunolocalized in distal tubules, whereas EGF receptor immunostaining was seen in proximal tubules cells. Vimentin immunostaining was confined to glomeruli and blood vessels. Tobramycin and cisplatin caused acute tubular necrosis in proximal convoluted tubules and proximal straight tubules, respectively. Tissue damage was accompanied by renal dysfunction reflected by an elevation of serum creatinine and BUN levels. Tubular necrosis was followed by a proliferative response indicative of tubular regeneration. Regenerative hyperplasia was associated with a reduction of total immunoreactive EGF due to a decrease of tissue-bound proEGF. Tubules undergoing regenerative repair were characterized by a disappearance of EGF receptors and the presence of immunoreactive vimentin. In tobramycin-treated rats, renal dysfunction lasted for 4-7 days and was fully reversible, as indicated by the return of serum markers to normal values.

Analysis of Variance↗
PubMed1993

Endogenous EGF as a potential renotrophic factor in ischemia-induced acute renal failure.

The time course for the increases in soluble renal epidermal growth factor (EGF) after ischemia has been established. These elevated levels of EGF have been compared with the degree of tissue injury as well as the extent of cell proliferation in the recovering tissue. Levels of soluble immunoreactive EGF (irEGF) in control animals were 9.74 +/- 1.1 ng/g wet wt (n = 4-8 for all values) and rose to 83.9 +/- 30 ng/g within 12 h after injury. Soluble irEGF content peaked at 88.8 +/- 15 ng/g at 24 h postinjury and returned to control values by 72 h. We previously reported that trypsin digestion of crude renal membranes (CRM) generates rat EGF that is indistinguishable from that isolated from the submandibular gland. Initial levels of trypsin-releasable membrane-associated irEGF were 439 +/- 26 ng/g. These levels fell to 46.6 +/- 9.6 ng/g at 48 h after injury. The total renal EGF demonstrated an 80% decline 48 h after injury but returned to 50% of the initial values after 72 h representing significant new synthesis of EGF-containing proteins between 48 and 72 h postinjury. Immunohistochemical staining of kidney paraffin sections for EGF immunoreactivity demonstrated staining intensities that paralleled the amount of irEGF in the trypsin-digested CRM fraction, suggesting that the membrane-associated irEGF is the predominant form detected by this technique. Regenerative hyperplasia subsequent to tubular insult was monitored by immunostaining nuclei of S phase cells after pulse labeling with the thymidine analogue 5-bromo-2'-deoxyuridine. Cell proliferation was particularly prominent in the outer stripe of outer medulla of kidneys exposed to ischemia and reached a maximum (19-fold higher than the baseline value) 48 h after reperfusion. Renal cell turnover returned to control values by day 7. The observation that the peak in soluble EGF levels (24 h) precedes the peak in tubular regeneration (48 h) by 24 h is consistent with the hypothesis that EGF is one of the mitogenic signals triggering regenerative hyperplasia after renal injury.

Acute Kidney Injury↗
PubMed1993

Morphometric and tridimensional studies of tubular cystic degeneration in rat kidney following exposure to cisplatin.

Cisplatin, a widely used chemotherapeutic agent, is characterized by a dose-limiting renal toxicity. Cystic tubular dilatation is the most typical histopathological alteration encountered in cisplatin-treated rats. The purpose of the present study was to explore by a morphometric approach the development of cystic degeneration and, in particular, to analyse, by computer-assisted tridimensional reconstructions, the spatial structure and the tubular origin of cisplatin-induced renal cysts. This study was performed on rats given 8 mg/kg cisplatin i.p. for four days and sacrificed 4, 7, 14, 21, 50 and 60 days after last drug administration. The relative area occupied by cystic tubules increased rapidly in the outer stripe of outer medulla (OSOM) and reached a maximum 21 days after the end of treatment. Cystic dilatations appeared later in the kidney cortex and the inner stripe of outer medulla (ISOM). The tridimensional study of cystic tubules located in OSOM confirmed previous reports indicating that they arise from proximal straight tubules and showed that cystic degeneration was not associated with atrophy or degeneration in more proximal parts of the nephron. Moreover, cystic tubules located in ISOM were found to originate from distal straight tubules and/or the loop of Henle, an observation which, to our knowledge, has not been reported so far in cisplatin-treated rats.

Animals↗
PubMed1992

Tubular injury and regeneration in the rat kidney following acute exposure to gentamicin: a time-course study.

Aminoglycoside antibiotics act as nephrotoxic drugs, inducing a lysosomal phospholipidosis and necrotic lesions essentially in convoluted proximal tubules. Previous studies have demonstrated that tubular injury caused by these compounds elicits a process of renal tissue repair (tubular regeneration) involving an increase of cell turnover in tubular epithelium. The present study was performed in order to: (i) achieve further insight into the temporal relationship between aminoglycoside-induced phospholipidosis, tubular necrosis, and tubular regeneration; and (ii) approach the control of tubular regeneration after nephrotoxin-induced insult. To investigate the latter point, we examined by immunocytochemistry the intrarenal distribution of epidermal growth factor (EGF) during tubular regeneration. Five groups of female Sprague-Dawley rats (n = 5) were treated for 4 days with gentamicin i.p. at a daily dose of 50 mg/kg delivered in 2 injections per day. Sham-treated animals (n = 5) received an equivalent amount of vehicle (0.9% NaCl) according to the same protocol. Groups of treated rats, and controls, were terminated 16 h (day 1), 4 days, 7 days, 14 days, and 21 days after the end of gentamicin administration. One hour prior to necropsy, each animal was given an i.p. injection of 40 mg 5-bromo-2'-deoxyuridine (BrdU) for the immunocytochemical demonstration of S-phase cells, using an anti-BrdU monoclonal antibody. Renal tissue was processed for light microscopy analysis, namely: a computer-aided morphometry of lysosomes in proximal tubular cells, a single-blind evaluation of gentamicin-induced tubular injury, the measurement of cell proliferation by immunocytochemical detection of BrdU-labeled nuclei, the demonstration of EGF-like immunoreactive material in renal tissue by using anti-rat EGF antiserum and immunogold-silver staining. As revealed by the morphometry of lysosomes in proximal tubular epithelium, the degree of gentamicin-induced phospholipidosis was maximum at day 1 (relative area occupied by lysosomes was increased 25-fold over mean control value) and declined thereafter. In contrast, tubular necrosis reached a peak 4 days after the end of drug administration. In proximal tubular epithelium, the stimulation of cell turnover associated with tubular regeneration showed a peak at day 7 (15-fold the mean control value). Tubular regeneration was also accompanied by mild interstitial hyperplasia. Three weeks after treatment with gentamicin, morphological evidence of drug-induced injury had disappeared due to the tissue repair process, except for the occasional presence of small hyperplastic foci in renal cortex interstitium. In both treated animals and controls, EGF immunoreactivity as revealed by immunocytochemical staining was associated with distal tubules (renal cortex and outer medulla).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Distribution of epidermal growth factor in the kidneys of rats exposed to amikacin.

The distribution of epidermal growth factor (EGF) was examined by immunocytochemistry in the kidneys of rats exposed to amikacin, an aminoglycoside antibiotic causing tubular necrosis at high dose. Five-animal groups were treated for 4 or 10 days with amikacin at daily doses of 15, 40, 80 or 200 mg/kg. The drug was delivered i.p. twice a day. One hour before termination, each rat received an i.p. injection of [3H] thymidine to evaluate DNA synthesis in renal tissue. After sacrifice, the kidneys were processed for morphological (semithin and paraffin sections) and biochemical analysis (measurement of DNA synthesis by [3H] thymidine incorporation in vivo). Amikacin induced in proximal tubules a dose-related lysosomal phospholipidosis, which was assessed by the morphometric evaluation of altered lysosomes ("myeloid bodies") on semithin section. However, frank evidence of acute tubular necrosis was only observed in rats receiving amikacin at a daily dose of 200 mg/kg. Concomitantly with the development of tubular necrosis, there was a rise in the rate of cell turnover, reflected by an increase of DNA synthesis in renal tissue. This sign of tubular regeneration was accompanied by a redistribution of EGF immunoreactivity, as revealed by immunocytochemical staining. Within renal cortex of control rats, EGF immunoreactivity predominantly appeared in distal tubules and collecting ducts (97% of examined tubular sections). In contrast, in treated animals where the renal cortex displayed evidence of tubular necrosis/regeneration, EGF immunoreactivity was frequently associated with proximal tubules (more than 30% of examined tubular sections, as compared to 3% in controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Amikacin↗
PubMed1985

The complete amino acid sequence of diphtheria toxin fragment B. Correlation with its lipid-binding properties.

The complete amino acid sequence of fragment B from diphtheria toxin has been determined. The polypeptide chain was split with cyanogen bromide, o-iodosobenzoic acid, clostripain and trypsin; all amino acid sequence analyses were made by automated Edman degradation. Fragment B, which corresponds to the carboxy terminus of the toxin molecule, contains 342 amino acids and has an Mr of 37240. The proposed amino acid sequence fully confirms the structure recently deduced from the nucleotide sequence of the structural gene. The complete sequence is analyzed in relationship with the role of fragment B in the transfer of diphtheria toxin fragment A from the extracellular medium into the cell cytoplasm.

Amino Acid Sequence↗
PubMed1982

The conformational properties of somatostatin. IV. The conformers contributing to the conformation equilibrium of somatostatin in aqueous solution as found by semi-empirical energy calculations and high-resolution NMR experiments.

The results of a conformational study by 1H and 13C high-resolution NMR at 270 and 500 MHz on the peptide hormone somatostatin have been compared with a series of conformers generated by semi-empirical energy calculations. The use of specifically deuterated phenylalanine residues has enabled us to confirm and supplement the identification of all but the phenylalanine aromatic resonances in the proton spectra of somatostatin. In order to minimize the risk of overlooking some low-energy conformations, four different strategies have been used for the generation of the conformers: two based on combinations of conformations of fragments that had been studied before, one on a random procedure and one on the conformational constraints existing in bicyclic analogs with high biological activity. The experimental values of 3JNH-C alpha H and 3J alpha beta coupling constants and the existence of several ring current shifts allowed us to select from the calculations those families of low-energy conformers that are compatible with the NMR results. The NH temperature coefficients do not warrant the existence of any stable beta or gamma turns in the molecule, although the region SRIF8-12 seems to be the most stable in this respect. In addition there are several upfield shifts: 0.2-0.4 ppm on the Lys9 side-chain, 0.3-0.5 ppm on the Phe6 alpha, beta and Phe7 alpha protons, as well as some 0.2-0.3 ppm shifts on parts of two phenylalanine ring systems. Almost all of these shifts decrease considerably with increasing temperature. Most of the observed NMR results are compatible with the properties of one family of low-energy conformations whose main features are a double beta II bend Trp8-Lys9, Thr10 -Phe11, a close proximity of the Trp8 and Lys9 side chains and an orientation of Phe7 towards the Phe6 alpha, beta protons. We conclude that this set of conformations forms a major contribution to the conformational equilibrium at room temperature. The properties of this and several other sets of low-energy conformations that do not dominate in aqueous solution are discussed in relation to al available experimental evidence.

Magnetic Resonance Spectroscopy↗
PubMed1982

Structure-activity relationships of the B fragment of diphtheria toxin: the lipid-binding domains.

Two different lipid-associating domains have previously been identified in diphtheria toxin fragment B: one of the surface type in the N-terminus of B and one of the transverse type in its middle region. We have now determined about 85% of the primary structure of fragment B and show, here, that the middle part of fragment B contains a highly hydrophobic region of 72 amino acid residues (polarity index: 295) which includes the transverse lipid-associating domain. That this domain is actually involved in a process of membrane penetration is suggested by lipid bilayer conductance measurements of the CNBr peptides of fragment B and trypsin treatment of fragment B-multilamellar liposome complexes.

Amino Acid Sequence↗