Fibrillary glomerulonephritis occurring in association with hereditary angioneurotic oedema, pernicious anaemia and hypothyroidism.
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Adult↗
Biomedical subjects
A Frankel
Publications and source records attributed to A Frankel.
Comparative clinical and physiological features of Maori, Pacific Islanders and Europeans with sleep related breathing disorders.
UNLABELLED: Recent studies have suggested that there is a familial association of sleep apnoea syndrome and that this is not entirely explained by inheritance of known risk factors. Maori (M) and Pacific Islanders (PI) have many of the body habitus features associated with sleep apnoea and therefore might be expected to exhibit more severe disease than Europeans (E). OBJECTIVE: To compare the clinical and physiological characteristics of the different ethnic groups and to determine if race was an independent predictor of severity of sleep apnoea. METHODOLOGY: A prospective evaluation of patients attending the Sleep Disordered Breathing Clinic which serves the whole of Auckland (population 1.1 million), New Zealand was conducted for the period July 1994 to August 1995. The evaluation included history including a 26 question questionnaire, Epworth sleepiness score, examination, and where indicated, full polysomnography. RESULTS: A total of 233 patients (154 E, 48 M and 33 PI), underwent full polysomnography. Forty-one (85%) of the M and 31 (94%) of PI had obstructive or mixed sleep apnoea compared with only 74 (49%) of the E (P < 0.0001; chi 2). There were few racial differences in the responses to the sleep questionnaire. M and PI were shown to have much greater neck and waist circumference and body mass indices. Severity parameters (apnoea-hypopnoea index, wake and minimum oxygen saturation, and apnoea duration) were greater for both M and PI compared with E (P < 0.001; Mann-Whitney U-test). Stepwise regression identified neck size, body mass index and age as independent predictors of severity. CONCLUSION: When other factors were controlled for, race was not an important independent predictor of severity of sleep apnoea.
Adult↗
Abrogation of taxol-induced G2-M arrest and apoptosis in human ovarian cancer cells grown as multicellular tumor spheroids.
Tumor cells grown as multicellular spheroids are known to be intrinsically more resistant to a large and diverse array of anticancer chemotherapeutic drugs compared to the same cells grown as dispersed monolayer cell cultures. Some drugs, however, seem relatively insensitive to this multicellular drug resistance, e.g., cisplatinum. Whether the cytotoxic effects of Taxol, an anticancer drug of growing importance in the treatment of breast and ovarian carcinomas, are diminished by multicellular growth conditions is unknown. To study this question, we examined the relative sensitivity of a panel of four different human ovarian carcinoma cell lines to either Taxol or cisplatinum. Upon exposure to Taxol, all the cell lines manifested a relative drug-resistant phenotype when grown as multicellular tumor spheroids, compared to the same cells grown as sparse monolayer cultures. This multicellular-dependent drug-resistant phenotype was not observed when the same cells were exposed to cisplatinum for an equivalent length of time. Monolayer but not spheroid cultures exposed to Taxol demonstrated an accumulation of cells at G2-M and a sub-G1 apoptotic region. In addition, Taxol-induced apoptosis was detected in monolayer conditions but not in the spheroid cultures. The relative sensitivity of the monolayer cell cultures was associated with a decrease in bcl-X(L) protein levels after Taxol exposure, an effect not observed in drug-exposed spheroids. Taken together, these results suggest that some aspects of intrinsic Taxol resistance in ovarian carcinoma may be due to multicellular-dependent or -associated mechanisms. This raises the possibility of using antiadhesive agents to reverse multicellular-dependent Taxol resistance in certain circumstances as a potential means of increasing the initial efficiency of Taxol therapy against ovarian carcinoma.
Antineoplastic Agents↗
Cholesterol emboli syndrome--uncommon or unrecognized?
Cholesterol emboli syndrome is a multisystem disorder that can be precipitated by angiographic procedures. We report 5 cases in which the presentation was renal failure. All patients had undergone angiography, but the temporal relation of the procedure to the clinical presentation was highly variable, the interval ranging from one day to four months. With the increase in diagnostic and therapeutic uses of angiography, the cholesterol emboli syndrome is likely to become more frequent and needs to be recognized.
Acute Kidney Injury↗
Double-site ricin B chain mutants retain galactose binding.
Three distinct double-site and two single-site ricin B chain (RTB) mutants were expressed in Spodoptera frugiperda insect cells and purified from infected cell supernatants. The yields of recombinant proteins were 0.01-0.2 mg/l. The purity after monoclonal antibody affinity chromatography was 1-20%. The mutant proteins were soluble, immunoreactive with monoclonal antibodies and polyclonal antibodies to RTB and demonstrated molecular weights of 32 kDa, similar to plant RTB. All three double-site and both single-site mutants bound asialofetuin and mammalian cell surfaces based on an asialofetuin ELISA and cell binding immunofluorescence assay. While one double-site mutant, W37S/Y248S, had a 1 log drop in sugar binding, the other two double-site mutants W37S/Y248H and D22E/D234E had 2 log reductions in sugar binding. Each mutant reassociated efficiently (25-75%) with plant ricin A chain (RTA) to form cytotoxic heterodimers. The concentration of protein required to reduce protein synthesis 50% (ID50) was 1 log higher than plant ricin for W37S/Y248S-RTA and the single-site mutant heterodimers, Q35N-RTA and D22E-RTA and 2 logs higher than plant ricin for the other two double-site mutant heterodimers. The results suggest amino acid residues in both the 1 alpha and 2 gamma subdomains of RTB participate in sugar binding. However, other subdomains must contribute to the avidity of ricin for cell surface oligosaccharides.
Animals↗
Cytotoxicity of KDEL-terminated ricin toxins correlates with distribution of the KDEL receptor in the Golgi.
DNAs encoding ricin toxin A chain (RTA), with or without a C-terminal endoplasmic reticulum retention signal KDEL, were subcloned into pGEX2T bacterial expression plasmid. After transformation of JM105 E. coli cells and induction with isopropylthio-beta-galactoside (IPTG), fusion proteins were bound to an immobilized glutathione matrix and recombinant ricin A chains released with thrombin. Both recombinant wild-type RTA and RTA with KDEL had immunological reactivity and catalytic activity indistinguishable from plant RTA. The bacterial RTA products reassociated with plant ricin B chain (RTB) similarly to plant RTA. Cell cytotoxicities were measured on seven cell lines for each A-chain and heterodimer. Although KDEL sequences enhanced cytotoxicity in most cases, significant variability was observed. In each case, addition of KDEL enhanced A-chain cytotoxicity more than holotoxin cytotoxicity. Three cell lines showed reduced KDEL enhancement of both RTA and ricin cytotoxicity. The concentration of KDEL receptor was examined on each cell line by immunofluorescence microscopy with an antireceptor monoclonal antibody. Differences in sensitivity to KDEL-containing toxins correlated with altered distribution of KDEL receptor between endoplasmic reticulum (ER) and Golgi compartments.
Amino Acid Sequence↗
Peptide and lipid growth factors decrease cis-diamminedichloroplatinum-induced cell death in human ovarian cancer cells.
Growth factors have been demonstrated to regulate the proliferation and viability of a number of cell lineages. Because most drugs used in chemotherapy kill cells through programmed cell death, by the process of apoptosis, we determined whether growth factors, specifically epidermal growth factor (EGF) and lysophosphatidic acid (LPA), which we have demonstrated recently to be a potent growth factor for ovarian cancer cells, would alter the ability of cis-diamminedichloroplatinum (cis-DDP), the most effective chemotherapeutic agent for ovarian cancer, to kill the HEY ovarian cancer cell line. We demonstrate that both EGF and LPA decrease the ability of cis-DDP to kill HEY ovarian cancer cells as assessed by colony-forming cell activity and dye reduction. Morphological changes, DNA release, and electron microscopy suggested that LPA and EGF protect ovarian cancer cells from programmed cell death induced by cis-DDP. Because LPA is present in high levels in ascitic fluid from ovarian cancer patients, and the EGF receptor is expressed by tumor cells from a significant portion of patients where it correlates with prognosis, growth factor modulation of cis-DDP-induced apoptosis may play a role in the poor prognosis associated with ovarian cancer.
Antineoplastic Agents↗
Rapamycin enhances apoptosis and increases sensitivity to cisplatin in vitro.
Apoptosis can be regulated in a number of different systems by the actions of cytokines. Rapamycin has been shown to exert its effects on growth factor-induced cell proliferation, at least in part, by blocking the activation of the p70 S6 kinase and thus preventing the downstream signaling process, such as the activation of the members of the cdk family. To determine whether this pathway plays a role in the regulation of apoptosis, we assessed the effect of rapamycin on apoptosis induced by interleukin 2 deprivation in murine T-cell lines, by T-cell receptor ligation in a murine T-cell hybridoma, by enforced c-myc expression in murine fibroblasts, and by corticosteroids in murine T-lymphoma cell lines. Although rapamycin did not induce apoptosis on its own, rapamycin augmented apoptosis in each of the cell lines used as indicated by increased genomic DNA fragmentation, decreased cell viability, and characteristic apoptotic changes in morphology. These results suggest that a signal transduction pathway(s) inhibited by rapamycin plays an important role in the susceptibility of cells to apoptosis. Many chemotherapeutic agents kill cancer cells through the induction of apoptosis. Strikingly, rapamycin increased the ability of the alkylating agent, cisplatin, to induce apoptosis in the human promyelocytic leukemia cell line HL-60 and the human ovarian cancer cell line SKOV3. These data suggest that a signal transduction pathway, likely related to p70 S6 kinase, inhibited by rapamycin may be an important component of the pathway which prevents cell death in many cell lineages and also indicate that rapamycin has the potential to augment the efficacy of selected anticancer therapies.
Animals↗
Glomerulonephritis associated with permanent pacemaker endocarditis.
Two patients with permanent transvenous cardiac pacemakers were seen with a history of pyrexia of unknown origin and renal failure. After extensive investigation both were found to have pacemaker endocarditis. A renal biopsy of one patient revealed changes characteristic of glomerulonephritis associated with this condition. Both patients underwent thoracotomy for open removal of their pacemaker and appropriate antibiotic treatment. One patient made a good recovery of renal function. Unfortunately the second patient died. These reports emphasize the need for vigilance for these two uncommon complications and the difficulty in their diagnosis.
Aged↗
Characterization of an ovarian cancer activating factor in ascites from ovarian cancer patients.
Ascites from ovarian cancer patients contain potent growth-promoting activity toward human ovarian cancer cells both in vitro and in vivo. This activity is associated with rapid increases in cytosolic free calcium ([Ca2+]i) as a consequence of phosphoinositide hydrolysis. In this study, we describe the purification, characterization, and identification of an ovarian cancer activating factor (OCAF) from ascites of ovarian cancer patients. We have isolated OCAF by a combination of solvent extraction, silica gel chromatography, and TLC. Mass spectral analysis, phospholipase sensitivity, and gas chromatographic behavior of purified OCAF indicate that OCAF is composed of various species of lysophosphatidic acid (LPA), including LPAs with polyunsaturated fatty acyl chains (linoleic, arachidonic, and docosahexaenoic acids). However, OCAF is more potent than sn-1 palmitoyl, oleoyl, or stearoyl LPA in increasing [Ca2+]i in ovarian cancer cells. The ability of OCAF to alter [Ca2+]i is sensitive to the effects of lipoxidase, whereas the activity of sn-1 oleoyl, stearoyl, or palmitoyl LPA is not, suggesting that polyunsaturated bonds in the fatty acyl chain of OCAF may account for its increased ability to activate ovarian cancer cells. Furthermore, a sn-2 linoleoyl LPA generated by phospholipase A1 treatment of synthetic phosphatidic acid is much more active than are sn-1 palmitoyl, stearoyl, or oleoyl LPA in increasing [Ca2+]i in ovarian cancer cells. Taken together, these data suggest that the ability of OCAF to increase cellular calcium may reside in the structure and/or location of the fatty acyl chain of LPA. Purified OCAF, at concentrations similar to those present in ascites from ovarian cancer patients, was sufficient to induce proliferation of ovarian cancer cells, as indicated by thymidine incorporation, reduction of 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, or colony formation. However, even at optimal concentrations of OCAF, proliferation was lower than that induced by FCS or ascites from ovarian cancer patients, indicating that, although OCAF may be a major regulator of ovarian cancer cells in vivo, it is not the sole mediator present in ascites, and it likely functions in concert with other growth factor activities.
Ascites↗
Expression of ricin B chain in Spodoptera frugiperda.
DNA encoding ricin B chain was derived from preproricin genomic DNA and ligated into the baculovirus transfer vector, pAcGP67A. Co-transfection of Spodoptera frugiperda Sf9 cells with BaculoGold DNA was followed by limiting dilution purification of recombinant baculovirus. Infection of SF9 cells at a multiplicity of infection of 1 in the presence of 25 mM lactose produced 3 mg/l of soluble, glycosylated, 34 kDa protein immunoreactive with monoclonal and polyclonal antibodies to ricin B chain. The recombinant ricin B chain had similar lectin-binding activity to plant ricin B chain. The recombinant protein reassociated with ricin toxin A chain similarly to ricin toxin B chain and the recombinant heterodimers had similar cell cytotoxicity to ricin.
Animals↗
Receptor subtype expression and responsiveness to bombesin in cultured human bronchial epithelial cells.
We detected low level expression of the gastrin-releasing peptide and neuromedin-B receptor mRNAs in cultures of human bronchial epithelium from 4 of 6 individuals. Bombesin receptor subtype-3 mRNA was undetectable in these cells. An elevation of intracellular calcium concentration was observed in response to bradykinin (6 of 6) and neurotensin (1 of 5) but not to bombesin (0 of 6), vasopressin (0 of 6), or cholecystokinin (0 of 3). In contrast, such responses are frequently noted in lung cancer cell lines. Bombesin did not stimulate the in vitro growth of an immortalized human bronchial epithelium cell line expressing low levels of bombesin receptor mRNAs. We conclude that bombesin receptors are expressed at low levels in human bronchial epithelium cells which may acquire greater responsiveness to multiple neuropeptides in the course of multistep carcinogenesis.
Base Sequence↗
Ethnic differences in the occurrence of the M1(ala213) haplotype of alpha-1-antitrypsin in asthmatic and non-asthmatic black and white South Africans.
An ethnic study of 175 individuals, comprising 65 black and 110 white South Africans, has shown a conclusive difference in the frequency of the M1(ala213) haplotype of alpha 1-antitrypsin (P < 0.00001). The M1(ala213) haplotype occurred more frequently in the black group. In the latter group, the frequency of the M1(ala213) haplotype was the same in both controls (0.55) and asthmatics (0.53). However, there was a significant difference in the frequencies (0.19 and 0.36) for the respective white groups (P < 0.01), the frequency of the M1(ala213) haplotype being much higher in the asthmatics. Apart from the above differences, there was also a difference in the elastase-inhibitory capacities of the homozygote phenotypes M1(val213) vs M1(ala213) (P < 0.0001), this capacity being lower in the latter phenotype. We conclude that the occurrence of the M1(ala213) allele of alpha 1-antitrypsin differs in various ethnic groups and may play a role in asthma.
Adult↗
Rickets presenting as stridor and apnea.
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Apnea↗
Renaturated ricin toxin B chain made in Escherichia coli is soluble, stable, and biologically active.
Escherichia coli cells transformed with plasmids containing ricin B-chain coding sequences are shown to express this heterologous protein in inclusion bodies. After denaturation and renaturation of the product in the presence of glutathione and lactose, the recombinant ricin B-chain is soluble, biologically active and stable. Cytotoxicity of heterodimer with this protein and ricin A-chain is bound to be only ten times less than of native ricin. Recombinant B-chain alone was nontoxic to cells (ID50 > 10(-6)M). Our data suggest that N-glycosylation of ricin B-chain is not required for its biological activity.
Cell Line↗
Quantitative SPECT of technetium-99m-DMSA uptake in the kidneys of normal children and in kidneys with vesicoureteral reflux: detection of unilateral kidney disease.
UNLABELLED: Quantitative SPECT was used to evaluate renal functional volume (cc), percent of injected dose/cc (%ID/cc) and renal uptake (%) in 11 children with unilateral vesicoureteral reflux grade 3 or greater, and in 19 normal control children without reflux. METHODS: Studies were performed 4-6 hr after intravenous injection of 0.750-2 mCi of 99mTc-DMSA. RESULTS: Control kidneys (n = 38) had a volume of 99.7 +/- 29.5 cc. The %ID/cc was 0.27 +/- 0.08, and the uptake in one kidney was 24.8% +/- 3.9%. Global renal uptake (right plus left) was 49.6% +/- 7.3%. Functional volume of the control kidneys showed an increase with age, and the %ID/cc showed a steeper decrease with age, resulting in a trend of the kidney uptake to decrease with age. Kidneys with reflux had a decreased kidney uptake of 15.7% +/- 29.5%, compared to age- and sex-matched controls (t = 4.7, p < 0.001). The contralateral kidneys without reflux had a significantly increased total uptake of 33.4% +/- 6.8% as compared to controls (t = 3.44, p < 0.01). Global uptake by the kidneys was 49.2% +/- 8.6% and was not statistically different from controls (t = 1.0, ns). CONCLUSION: Our results suggest that SPECT quantitation of 99mTc-DMSA uptake in each kidney separately could be used as a noninvasive method to assess impairment and compensation of the function of the individual kidney in children with vesicoureteral reflux.
Aging↗
Protein kinase C is not involved in the homologous desensitization of bombesin responses in small cell lung cancer cells.
Homologous desensitization of responses to bombesin in small cell lung cancer cells can be mimicked by protein kinase C-activating phorbol esters. We show that phorbol ester-induced desensitization can be blocked by prior treatment with the protein kinase C inhibitor staurosporine or prolonged pretreatment with phorbol esters. However, under these conditions, homologous desensitization to bombesin persists. These data indicate that phorbol ester-induced desensitization is distinguishable from bombesin-induced homologous desensitization. Protein kinase C is not a dominant component in the homologous desensitization to bombesin in small cell lung cancer cells.
Alkaloids↗
Factors associated with airway colonisation and invasion due to Klebsiella spp.
The clinical significance of a heavy growth of Klebsiella spp. in sputum was studied in 54 patients. All but 3 patients had significant factors potentially associated with respiratory tract colonisation or invasion. Risk factors identified for colonisation of the airway and for invasive disease were similar. Patients with community-acquired Klebsiella infections were more likely to have underlying chronic respiratory diseases. Prior antibiotic use was a risk factor for nosocomial infections which occurred more commonly with antibiotic-resistant organisms. The most common diagnoses were airway colonisation, acute community-acquired chest infections, and nosocomial chest infections. Primary acute community-acquired pneumonia was uncommon. The sensitivity and specificity of the sputum Gram stain (in the setting of positive sputum cultures) in suggesting the presence of invasive disease due to Klebsiella spp. were 42% and 69% respectively.
Adolescent↗