Biomedical subjects

J Allen

Publications and source records attributed to J Allen.

At least 55 records · Page 3Linked to original sources

PubMed2001

Features of carnitine palmitoyltransferase type I deficiency.

Carnitine palmitoyltransferase type I (CPT I) is unique among long-chain fatty acid oxidation enzymes in that there are two tissue-specific isoforms, 'hepatic' and 'muscle', which are encoded by two separate genes. The 'hepatic' isoform is expressed in liver, kidney and fibroblasts and at low levels in the heart, while the other isoform occurs in skeletal muscle and is the predominant form in heart. Reported patients with CPT I deficiency lack activity of the hepatic isoform and present before 30 months of age with hypoketotic hypoglycaemia, hepatomegaly with raised transaminases, seizures and coma. We discuss four new cases in three families showing, variously, renal tubular acidosis, transient hyperlipidaemia and, paradoxically, myopathy with elevated creatinine kinase or cardiac involvement in the neonatal period as additional features that deserve wider recognition.

Acidosis, Renal Tubular↗

PubMed2001

A clinical study of the Korotkoff phases of blood pressure in children.

BACKGROUND: Five Korotkoff phases are described in adults, but there are no studies of the Korotkoff phase distribution in children. This study determines the presence and length of Korotkoff phases in children, providing data on the repeatability of these measurements, the relationship between the phases, and finally the relationship between the phases and heart rate, blood pressure and arm circumference. METHODS: Seventy, 11-year-old children were studied. The Korotkoff sounds were recorded from the bell of a stethoscope to a MiniDisc system and each sound described twice on separate occasions as phase I, II, III or IV, with phase V meaning disappearance of the sound. RESULTS: Phases I, II, III, IV and V were present in 97% (68/70), 61% (43/70), 51% (36/70), 88% (62/70) and 80% (56/70) respectively. When the recordings were blindly re-assessed there was no significant difference in the phase distribution of the sounds. All five phases were present in 40% (28/70). Phase III only occurred in the presence of phase II (P < 0.0001). There was no significant relationship between the presence of the different phases and heart rate or blood pressure. Arm circumference was significantly larger in children with phase V present (P < 0.02). CONCLUSIONS: The Korotkoff sounds and phase distribution present in normal children is described. Korotkoff sounds were consistently allocated to the various Korotkoff phases. This study provides insights into the problems of accurate diastolic blood pressure measurement. Phase V was more likely to be present with increasing arm circumference, but the variation in the occurrence of phases II and III remains unexplained.

Arm↗

PubMed2001

Assessment of skin basement membrane zone antibodies in the urine of patients with acquired subepidermal immunobullous diseases.

BACKGROUND: In bullous pemphigoid (BP), cicatricial pemphigoid (CP) and linear IgA disease (LAD), autoantibodies to the basement membrane zone (BMZ) are found in skin and mucosa, blood and blister fluid. OBJECTIVES: To assess whether BMZ antibodies might also be detected in urine. METHODS: Urine and serum samples from 62 patients (32 with BP, 17 with CP and 13 with LAD) were analysed for antibody isotypes and subclasses by indirect immunofluorescence, and urine and serum samples from 40 patients (25 with BP, eight with CP and seven with LAD) were screened for target antigens using immunoblotting. RESULTS: Fourteen of 32 patients with BP had detectable levels of IgG BMZ autoantibodies in their urine, and all 32 had positive sera. Of these 14 BP patients, 13 had epidermal-binding serum autoantibodies at a titre > 1 : 160, and one had dermal-binding serum antibodies at a titre of 1 : 40. BMZ autoantibodies were not detected in the urine of the CP or LAD patients, but the corresponding sera were of low titre or negative. IgG subclasses (IgG1-4) were less frequently detected in urine than in serum. IgG4 was the predominant subgroup found (10 urine samples and all 14 sera), followed by IgG1 (two urine samples and 12 sera); IgG2 was detected in a single urine sample and three sera, and IgG3 was not detected. Eight of 25 BP and one of eight CP urine samples were positive on immunoblotting, and bound BP230 and/or BP180 with IgA and/or IgG autoantibodies. IgA autoantibodies were not detected in the urine of the seven LAD patients. The corresponding sera were often more positive, with 21 of 25 BP, five of eight CP and six of seven LAD sera immunoblotting the major BP antigens. CONCLUSIONS: The detection of IgG autoantibodies from urine samples using indirect immunofluorescence correlated with a high titre of IgG autoantibodies in the serum. IgG and IgA autoantibodies in the urine were detected by immunoblotting, although less frequently than in serum. The finding of BMZ antibodies in the urine of many BP patients may have clinical relevance, and may have a restricted application in the diagnosis of immunobullous disease.

Adult↗

PubMed2001

Mixed immunobullous disease of childhood: a good response to antimicrobials.

BACKGROUND: Immunobullous diseases are uncommon in childhood. In contrast to adults, the most commonly seen is IgA-mediated chronic bullous disease of childhood (CBDC), while IgG-mediated bullous pemphigoid (BP), cicatricial pemphigoid (CP) and epidermolysis bullosa acquisita (EBA) are rare. We have demonstrated both IgG and IgA autoantibodies to basement membrane zone target antigens in eight children with 'mixed immunobullous disease of childhood'. OBJECTIVES: To elucidate whether a dual antibody response makes these patients distinct regarding their presentation, immunopathology, course and prognosis. METHODS: We compared the eight children showing the double antibody response with 62 children with CBDC, BP, CP and EBA in whom only one antibody isotype was demonstrated. Clinical information at presentation, clinical course and response to treatment were recorded, and immunoblotting and direct and indirect immunofluorescence (IF) were performed. RESULTS: Six of the eight patients presented with clinical features of CBDC. In two others, it was uncertain whether they had CBDC or BP. Seven of the eight demonstrated a dual antibody response on indirect IF and three on direct IF. Immunoblotting revealed a variety of epidermal and dermal target antigens (BP230, BP180, 97-kDa protein and laminin 5). Five of the eight responded well to dapsone, two to sulphonamides, and one to systemic erythromycin alone. The clinical course was not protracted. Five are in remission 1-4 years following treatment, and three still have active disease suppressed by treatment after 6 months-2 years. CONCLUSIONS: Although we do not know why these children have 'mixed immunobullous disease' (the dual antibody response), our results indicate that the presence of IgA is associated with a good response to treatment with antimicrobials (dapsone, sulphonamides, erythromycin), and the clinical course is no more protracted than that found in children with a single antibody response.

Anti-Infective Agents↗

PubMed2001

Paraneoplastic pemphigus: an association with fludarabine?

Paraneoplastic pemphigus is a relatively recently described immunobullous disease with characteristic features. We report three cases of paraneoplastic pemphigus in adult men with chronic lymphocytic leukaemia arising within a week of completion of treatment with fludarabine. In all cases, withdrawal of fludarabine and treatment of the blistering was associated with marked cutaneous improvement. Fludarabine, a synthetic nucleoside analogue, which has only been available in Britain since 1994, is known to be associated with autoimmune phenomena and may have been involved in the development of paraneoplastic pemphigus in these cases.

Antineoplastic Agents↗

PubMed2001

Vancomycin-induced linear IgA disease with autoantibodies to BP180 and LAD285.

Linear IgA disease (LAD) is an acquired autoimmune subepidermal bullous disease characterized by the linear deposition of IgA at the basement membrane zone. A minority of cases are induced by drugs, of which the most frequently implicated is vancomycin. The target antigens in idiopathic LAD are heterogeneous, but have not previously been reported in vancomycin-induced LAD. We report three cases, and in two of these we investigated the target antigens. In both we identified IgA antibodies to LAD285 and IgA and IgG antibodies (dual response) to BP180.

Aged↗

PubMed2001

Bullous pemphigoid in pregnancy: contrasting behaviour in two patients.

Bullous pemphigoid (BP) is an increasingly common immunobullous disease of the elderly, and, due to the late age of onset, is rarely seen in women of fertile age. Consequently, to the best of our knowledge no cases of BP in pregnancy have been described. We present two cases of BP that have differed in disease behaviour during pregnancy.

Adult↗

PubMed2001

Casualization of the nursing workforce: a New Zealand perspective on an international phenomenon.

A discussion of the increased use of 'casual' nursing staff (those nurses employed on a casual or 'per diem' basis) is presented. Reference is made to related literature, together with consideration of the implications associated with this trend. This issue has international significance, with the increased use of casual staff being widely recognised. A New Zealand perspective is included, with the provision of nursing care at Christchurch Hospital presented to illustrate certain aspects of the discussion. The impact of changing health-care systems and increased emphasis on efficiency and accountability are identified. This change to workplace practice will inevitably affect nursing; possible future developments are considered.

Efficiency, Organizational↗

PubMed2001

ST depression only on the initial 12-lead ECG: early diagnosis of acute myocardial infarction.

AIMS: To compare the diagnostic ability of the 12-lead ECG with body surface mapping for early detection of acute myocardial infarction in patients presenting with ST depression only on the 12-lead ECG. METHODS AND RESULTS: Fifty-four consecutive patients with chest pain <24 h and ST depression were recruited. A 12-lead ECG and 80-lead body surface map were recorded at presentation from which univariate and multivariate prediction models of acute myocardial infarction were developed. Patients were randomly divided into a training-set and a validation-set. Acute myocardial infarction occurred in 16/30 training-set and 8/24 validation-set patients. Univariate prediction of acute myocardial infarction by the 12-lead ECG, based on the depth or numbers of leads with ST depression, was not improved by assessment of ST elevation outside the conventional 12 leads using body surface mapping. The optimum multivariate 12-lead ECG model developed in training-set patients (six ST depression variables) had poor sensitivity (38%) although good specificity (81%) for acute myocardial infarction when tested prospectively in validation-set patients. In contrast, the optimum body surface mapping model developed in training-set patients (three isointegral or isopotential variables) achieved high sensitivity (88%) whilst maintaining good specificity (75%) for acute myocardial infarction when tested prospectively in validation-set patients. CONCLUSION: Body surface mapping, when compared with the 12-lead ECG, may improve the early diagnosis of acute myocardial infarction in patients presenting with chest pain and ST depression only on the 12-lead ECG.

Aged↗

PubMed2001

Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabine.

DepoCyte is a slow-release formulation of cytarabine designed for intrathecal administration. The goal of this multi-centre cohort study was to determine the safety and efficacy of DepoCyte for the intrathecal treatment of neoplastic meningitis due to breast cancer. DepoCyte 50 mg was injected once every 2 weeks for one month of induction therapy; responding patients were treated with an additional 3 months of consolidation therapy. All patients had metastatic breast cancer and a positive CSF cytology or neurologic findings characteristic of neoplastic meningitis. The median number of DepoCyte doses was 3, and 85% of patients completed the planned 1 month induction. Median follow up is currently 19 months. The primary endpoint was response, defined as conversion of the CSF cytology from positive to negative at all sites known to be positive, and the absence of neurologic progression at the time the cytologic conversion was documented. The response rate among the 43 evaluable patients was 28% (CI 95%: 14-41%); the intent-to-treat response rate was 21% (CI 95%: 12-34%). Median time to neurologic progression was 49 days (range 1-515(+)); median survival was 88 days (range 1-515(+)), and 1 year survival is projected to be 19%. The major adverse events were headache and arachnoiditis. When drug-related, these were largely of low grade, transient and reversible. Headache occurred on 11% of cycles; 90% were grade 1 or 2. Arachnoiditis occurred on 19% of cycles; 88% were grade 1 or 2. DepoCyte demonstrated activity in neoplastic meningitis due to breast cancer that is comparable to results reported with conventional intrathecal agents. However, this activity was achieved with one fourth as many intrathecal injections as typically required in conventional therapy. The every 2 week dose schedule is a major advantage for both patients and physicians.

Adult↗

PubMed2001

Relation between heart rate and pulse transit time during paced respiration.

Pulse transit time (PTT) is a simple, non-invasive measurement, defined as the time taken from a reference time for the pulse pressure wave to travel to the periphery. PTT is influenced by heart rate, blood pressure changes and the compliance of the arteries, but few quantitative data are available describing the factors which influence PTT. The aim of this study was to investigate the relationship between the cardiac beat-to-beat interval (RR) and PTT, using paced respiration to generate changes in both variables. We analysed PTT and RR interval from 15 normal healthy subjects during paced breathing, and the cross-correlation function between PTT and RR was used to quantify their relationship. Over the 15 subjects, the maximum change in PTT ranged from 7 to 23 ms with a mean +/- standard deviation of 14 +/- 5 ms, and that in RR interval from 86 to 443 ms (241 +/- 102 ms). Examining changes over time, the best correlation (r = +0.69, p < 0.01) was obtained when PTT was advanced relative to RR, with a change in RR followed by a corresponding change in PTT 3.17 +/- 0.76 beats later. We conclude that there is a strong relationship between PTT changes and RR interval changes, but these changes are not in phase.

Adult↗

PubMed2001

Neoplastic transformation of human osteoblast cells to the tumorigenic phenotype by heavy metal-tungsten alloy particles: induction of genotoxic effects.

Heavy metal-tungsten alloys (HMTAs) are dense heavy metal composite materials used primarily in military applications. HMTAs are composed of a mixture of tungsten (91-93%), nickel (3-5%) and either cobalt (2-4%) or iron (2-4%) particles. Like the heavy metal depleted uranium (DU), the use of HMTAs in military munitions could result in their internalization in humans. Limited data exist, however, regarding the long-term health effects of internalized HMTAs in humans. We used an immortalized, non-tumorigenic, human osteoblast-like cell line (HOS) to study the tumorigenic transforming potential of reconstituted mixtures of tungsten, nickel and cobalt (rWNiCo) and tungsten, nickel and iron (rWNiFe). We report the ability of rWNiCo and rWNiFe to transform immortalized HOS cells to the tumorigenic phenotype. These HMTA transformants are characterized by anchorage-independent growth, tumor formation in nude mice and high level expression of the K-ras oncogene. Cellular exposure to rWNiCo and rWNiFe resulted in 8.90 +/- 0.93- and 9.50 +/- 0.91-fold increases in transformation frequency, respectively, compared with the frequency in untreated cells. In comparison, an equivalent dose of crystalline NiS resulted in a 7.7 +/- 0.73-fold increase in transformation frequency. The inert metal tantalum oxide did not enhance HOS transformation frequency above untreated levels. The mechanism by which rWNiCo and rWNiFe induce cell transformation in vitro appears to involve, at least partially, direct damage to the genetic material, manifested as increased DNA breakage or chromosomal aberrations (i.e. micronuclei). This is the first report showing that HMTA mixtures of W, Ni and Co or Fe cause human cell transformation to the neoplastic phenotype. While additional studies are needed to determine if protracted HMTA exposure produces tumors in vivo, the implication from these in vitro results is that the risk of cancer induction from internalized HMTAs exposure may be comparable with the risk from other biologically reactive and insoluble carcinogenic heavy metal compounds (e.g. nickel subsulfide and nickel oxide).

Alloys↗

PubMed2001

3-Hydroxyisobutyric aciduria: phenotypic heterogeneity within a single family.

3-Hydroxyisobutyric aciduria is a rare biochemical finding associated with a variable clinical phenotype in the literature. We report two siblings excreting abnormal levels of this metabolite from a consanguineous family who manifested distinct phenotypic variation. We speculate as to whether this biochemical anomaly may simply be an incidental finding and suggest that pre-natal counselling on the basis of metabolite identification may be unwarranted.

Child↗

PubMed2001

Mechanisms of contrast agent destruction.

Various applications of contrast-assisted ultrasound, including blood vessel detection, perfusion estimation, and drug delivery, require controlled destruction of contrast agent microbubbles. The lifetime of a bubble depends on properties of the bubble shell, the gas core, and the acoustic waveform impinging on the bubble. Three mechanisms of microbubble destruction are considered: fragmentation, acoustically driven diffusion, and static diffusion. Fragmentation is responsible for rapid destruction of contrast agents on a time scale of microseconds. The primary characteristics of fragmentation are a very large expansion and subsequent contraction, resulting in instability of the bubble. Optical studies using a novel pulsed-laser optical system show the expansion and contraction of ultrasound contrast agent microbubbles with the ratio of maximum diameter to minimum diameter greater than 10. Fragmentation is dependent on the transmission pressure, occurring in over 55% of bubbles insonified with a peak negative transmission pressure of 2.4 MPa and in less than 10% of bubbles insonified with a peak negative transmission pressure of 0.8 MPa. The echo received from a bubble decorrelates significantly within two pulses when the bubble is fragmented, creating an opportunity for rapid detection of bubbles via a decorrelation-based analysis. Preliminary findings with a mouse tumor model verify the occurrence of fragmentation in vivo. A much slower mechanism of bubble destruction is diffusion, which is driven by both a concentration gradient between the concentration of gas in the bubble compared with the concentration of gas in the liquid, as well as convective effects of motion of the gas-liquid interface. The rate of diffusion increases during insonation, because of acoustically driven diffusion, producing changes in diameter on the time scale of the acoustic pulse length, thus, on the order of microseconds. Gas bubbles diffuse while they are not being insonified, termed static diffusion. An air bubble with initial diameter of 2 microns in water at 37 degrees C is predicted to fully dissolve within 25 ms. Clinical ultrasound contrast agents are often designed with a high molecular weight core in an attempt to decrease the diffusion rate. C3F8 and C4F10 gas bubbles of the same size are predicted to fully dissolve within 400 ms and 4000 ms, respectively. Optical experiments involving gas diffusion of a contrast agent support the theoretical predictions; however, shelled agents diffuse at a much slower rate without insonation, on the order of minutes to hours. Shell properties play a significant role in the rate of static diffusion by blocking the gas-liquid interface and decreasing the transport of gas into the surrounding liquid. Static diffusion decreases the diameter of albumin-shelled agents to a greater extent than lipid-shelled agents after insonation.

Animals↗

PubMed2001

Treatment of canine leproid granuloma syndrome: preliminary findings in seven dogs.

OBJECTIVE: To determine effective treatment strategies for patients with refractory canine leproid granuloma syndrome. DESIGN: Multi-institutional retrospective/prospective case series using client-owned dogs. PROCEDURE: Seven dogs (four Boxers, one Dobermann, one Bullmastiff and one Bullmastiff cross-bred; ages 3 to 11 years) with leproid granulomas were treated successfully using a variety of treatment regimens. These cases were recruited because: lesions were either widely distributed over the dog; progressive, despite routine therapy, or were associated with particularly disfiguring lesions. The treatment regimen evolved during the course of the clinical study. RESULTS: Combination therapy using rifampicin (5 to 15 mg/kg p.o., every 24 h) and clarithromycin (8 to 24 mg/kg p.o. daily; dose divided every 8 or every 12 h) was used most frequently and proved to be effective and free from side effects. Total daily doses of clarithromycin in excess of 14 mg/kg were considered optimal and long treatment courses, in the order of 1 to 3 months, were used. Combination therapy using rifampicin (25 mg/kg; that is, higher than the recommended dose) and clofazimine was effective in one case, but resulted in hepatotoxicity. A topical formulation of clofazimine in petroleum jelly was used as an adjunct to oral rifampicin and doxycycline in another patient treated successfully. CONCLUSION: Based on our evolving clinical experience, a combination of rifampicin (10 to 15 mg/kg p.o., every 24 h) and clarithromycin (15 to 25 mg/kg p.o. total daily dose; given divided every 8 to 12 h) is currently recommended for treating severe or refractory cases of canine leproid granuloma syndrome. Treatment should be continued (typically for 4 to 8 weeks) until lesions are substantially reduced in size and ideally until lesions have resolved completely. A topical formulation, containing clofazimine in petroleum jelly may be used as an adjunct to systemic drug therapy. Further work is required to determine the most cost effective treatment regimen for this condition.

Animals↗

PubMed2001

Practical aspects of in situ 16O (gamma,n) 15O activation using a conventional medical accelerator for the purpose of perfusion imaging.

We report investigations into the feasibility of generating radioactive oxygen (15O, a positron emitter, with half-life 2.05 min) using a tuned Elekta SL25 accelerator, for the end purpose of imaging tumor perfusion. 15O is produced by the "gamma, neutron," (gamma,n) reaction between high-energy photons and normal oxygen (16O) in the body. As most in vivo 16O is bound in water molecules the 15O radio-marker is produced in proportion to water content in tissue. Imaging the washout of the 15O distribution using sensitive positron-emission-tomography (PET) technology can yield spatial information about blood perfusion in the tissue. The aim of this article was to determine the amount of 15O activity that could be produced by the tuned medical accelerator. A further aim was to model the activation process using Monte Carlo and to investigate ways to optimize the amount of 15O that could be generated. Increased activation was achieved by (i) tuning the beam to give higher-energy electrons incident on the target of the accelerator, (ii) increasing dose rate by removing the conventional filtration in the beam and reducing the source to object distance, and (iii) reducing low-energy photons by means of a carbon block absorber. The activity per-unit-dose produced by the tuned beam was measured by irradiating spheres of water to known doses and placing the spheres in a calibrated coincidence-counting apparatus. Peak energy of the tuned bremsstrahlung beam was estimated at 29 MeV, and generated activity up to 0.24/microCi/cc/3Gy in water. The measured amount of 15O agreed to within 10% of the prediction from the Monte-Carlo-computed spectrum, indicating reasonable ability to model the activation process. The optimal thickness of the carbon absorber was found to be about 25 cm. The insertion of a carbon absorber improved spectral quality for activation purposes but at the cost of reduced dose rate. In conclusion, the viability of generating 15O with an Elekta SL25 has been demonstrated. In conjunction with recent advances in high-sensitivity portable PET imaging devices, real potential exists for imaging in situ activated 15O washout as a surrogate measurement of macroscopic tumor perfusion.

Calibration↗

PubMed2001

Mitral regurgitation after anthracycline treatment for childhood malignancy.

OBJECTIVE: To investigate the new onset of mitral regurgitation in patients with otherwise normal echocardiograms after anthracycline treatment and to assess its relation to other selected indicators of myocardial damage. DESIGN: Prospective echocardiographic and electrocardiographic study. SETTING: Tertiary paediatric cardiac referral centre. PATIENTS: 305 patients, aged 2-33 years (median 14 years), treated with cumulative anthracycline doses of between 150-450 mg/m(2) (median 180 mg/m(2)) for childhood malignancy. MAIN OUTCOME MEASURES: Colour flow Doppler detection of mitral regurgitation and its relation to changes in echocardiographic indices of left ventricular function (systolic and diastolic dimensions, fractional shortening) and to changes in the 12 lead ECG; and the prevalence of mitral regurgitation in the anthracycline treated patients in comparison with previously studied normal volunteers of similar age. RESULTS: 34 patients (11.6%) developed ultrasound detectable mitral regurgitation, which was not apparent clinically, during or after anthracycline treatment, compared with only 1.8% of a normal population of similar age (p < 0.0001). Nine of the 34 also developed non-specific T wave abnormalities. All 34 patients had normal systolic function at the time of initial detection of mitral regurgitation, but four later developed impaired left ventricular function (5, 11, 20, and 27 months after the first detection of mitral regurgitation). CONCLUSIONS: Mitral regurgitation occurs much more often in patients treated with anthracyclines than in the normal population. Echocardiographic detection of new mitral regurgitation with or without ECG abnormalities may be an early predictor of anthracycline cardiomyopathy.

Adolescent↗

PubMed2001

Subcellular localization of bilirubin in rat brain after in vivo i.v. administration of [3H]bilirubin.

Bilirubin appears to be toxic in vitro to several cellular functions localized to different subcellular compartments. It would therefore be useful to know what concentrations of bilirubin might be found in cell organelles in vivo. Rats were anesthetized and allocated to one of three groups: control, hypercarbia, and hyperosmolality. Each rat received a 5-min bolus dose of bilirubin 50 mg/kg i.v. (containing approximately 200 microCi [(3)H]bilirubin). Rats were killed 10 or 30 min after the start of the bilirubin infusion. Each brain was homogenized, and subcellular fractions were isolated by high-speed gradient centrifugation in sucrose media. The gradients were separated into aliquots of 2 mL, and the protein content was determined in each aliquot. Radioactivity was determined by scintillation counting, and the content of bilirubin per milligram of protein was calculated. Statistical comparisons were performed with Kruskal-Wallis nonparametric ANOVA. There were highly significant differences in bilirubin content per milligram of protein among subcellular compartments in all groups and at both time points. In all groups there were relatively high concentrations of bilirubin in the myelin fraction, an interesting observation in light of the theory that membranes are the primary target of bilirubin toxicity. The very high concentration of bilirubin relative to protein in cytoplasm, ribosomes, and mitochondria in the hyperosmolar group are also notable in light of data from hyperbilirubinemic animals in which changes in electrophysiology or energy metabolism only appeared after hyperosmolar opening of the blood-brain barrier. The present data may be useful in planning in vitro studies of bilirubin toxicity in cell organelles.

Animals↗