Biomedical subjects

R Tanaka

Publications and source records attributed to R Tanaka.

At least 19 recordsLinked to original sources

PubMed1992

Calpain may produce a Ca(2+)-independent form of kinase C in long-term potentiation.

Both an enhancement of Ca(2+)-independent kinase activity in the supernatant fraction and enhanced breakdown of type beta kinase C (PKC-beta) were observed in the hippocampus after induction of tetanus-induced long-term potentiation (LTP) in the hippocampal CA1 region of rat. The enhanced activity was inhibited by the PKC-specific inhibitor, PKC19-36. Both phenomena were also observed simultaneously in the in vitro model system in which hippocampal homogenate was treated with CaCl2, and both enhancements were inhibited by the addition of calpain inhibitors, leupeptin and benzyloxycarbonyl-Leu-Met-H. The results suggest that Ca(2+)-independent kinase activity enhanced in the supernatant fraction during LTP derives from the catalytic fragment of PKC-beta released by calpain.

Animals↗

PubMed1992

Ca(2+)-binding proteins in rat synaptic fractions surveyed by the 45Ca2+ overlay method.

Ca(2+)-binding proteins in the synaptic and subsynaptic fractions (P2, synaptosome, synaptic plasma membrane, and postsynaptic density [PSD]-enriched fractions) and soluble fraction of rat brain were surveyed by a 45Ca2+ overlay method. The PSD-enriched fraction from cerebral cortex contained two major Ca(2+)-binding proteins (55,000 M(r) and 19,000 M(r)) and a distinct group (in 140,000 M(r) region), and two minor ones (66,000 M(r) and 16,000 M(r)); and the fraction from cerebellum contained two (55,000 M(r) and 19,000 M(r)). The proteins with 55,000 M(r) and 19,000 M(r) were identified as tubulin and calmodulin, respectively, and present in all the fractions investigated. The Ca(2+)-binding proteins of 140,000 M(r) region were found only in the PSD-enriched fraction isolated from cerebral cortex: neither the PSD-enriched fraction isolated from cerebellum nor other subcellular fractions prepared from cerebral cortex and cerebellum contained the proteins. The 140,000 M(r) Ca(2+)-binding proteins were the substrates for the Ca2+/calmodulin-dependent protein kinase II associated with PSD, and no change in the Ca(2+)-binding was detected by the 45Ca2+ overlay method after phosphorylation of the proteins by the protein kinase. The 16,000 M(r) Ca(2+)-binding protein might be the beta-subunit of calcineurin. Calretinin and calbindin-D28k were also detected as Ca(2+)-binding proteins in the soluble fractions of both cerebral cortex and cerebellum.

Animals↗

PubMed1992

Stem cell factor enhances proliferation, but not maturation, of murine megakaryocytic progenitors in serum-free culture.

The effects of recombinant rat stem cell factor (SCF/c-kit ligand) on murine megakaryocytopoiesis were studied using partially purified bone marrow cells derived from normal and 5-fluorouracil (5-FU)-treated mice in a serum-free culture system. SCF alone did not support the formation of megakaryocyte (M) and granulocyte-macrophage-megakaryocyte (GMM) colonies. However, the addition of SCF to cultures containing interleukin-3 (IL-3) resulted in a significant increase in the number of M and GMM colonies formed by bone marrow cells from normal mice, whereas IL-6 augmented only M colony growth. The stimulatory effect of SCF was approximately three to four times as high as that of IL-6 on the primitive progenitors capable of megakaryocytic-lineage expression derived from 5-FU-treated mice. In addition, SCF, but not IL-6, significantly increased the number of constituent cells in the individual M colonies supported by IL-3. On the other hand, SCF did not exert any effect on the size and DNA content of megakaryocytes in IL-3-dependent M and GMM colonies, whereas IL-6 enhanced the maturation of megakaryocytes. These results suggest that SCF stimulates the proliferative process in megakaryocytic progenitors and that the main activity of IL-6 is the promotion of megakaryocyte maturation.

Animals↗

PubMed1992

Antibody specific for the Thr-286-autophosphorylated alpha subunit of Ca2+/calmodulin-dependent protein kinase II.

We report the production of an antibody specific for Ca2+/calmodulin-dependent protein kinase II (CaM-KII) autophosphorylated only at Thr-286 of the alpha subunit. Peptide Y-66 [sequence MHRQETVDC (Met-281 to Cys-289 of alpha subunit of CaM-KII)] was synthesized and phosphorylated by the CaM-KII endogenous to synaptic cytoskeleton (postsynaptic density-enriched fraction); the phosphorylated amino acid residue threonine corresponds to Thr-286 in the kinase alpha subunit. The phosphorylated Y-66 peptide was separated from the unphosphorylated peptide by HPLC and used as an immunogen after being coupled to hemocyanin. The antibodies that reacted with hemocyanin and unphosphorylated Y-66 peptide were adsorbed, and then IgG was purified. ELISA proved that the IgG obtained reacted specifically with phosphorylated Y-66 peptide. Immunoblot analysis showed that the antibody reacted specifically to the autophosphorylated CaM-KII both in purified and synaptic cytoskeleton-associated form. Appearance of CaM-KII subunits immunoreactive to anti-phosphorylated Y-66 antibody paralleled the generation of Ca(2+)-independent kinase activity. Immunocytochemical experiments clearly showed expression of the Thr-286- or Thr-287-autophosphorylated form of CaM-KII in cultured hippocampal cells treated with N-methyl-D-aspartate. Thus, this antibody could be extremely useful for studying the biological functions of CaM-KII.

Amino Acid Sequence↗

PubMed1992

Cloning of cDNAs encoding human S-100 alpha and beta subunits and their differential expression in human tumor cell lines.

We isolated nearly full-length clones of S-100 alpha and beta subunit cDNAs from a human brain cDNA library. The alpha subunit cDNA was 579 bp long and contained 99 bp of 5'-noncoding region, 282 bp of coding region, and 198 bp of 3'-noncoding region. The beta subunit cDNA was 743 bp long and contained 57 bp of 5'-noncoding region, 276 bp of coding region, and 410 bp of 3'-noncoding region. An amino acid sequence comparison between human and bovine alpha subunits and between human and rat beta subunits showed that both subunits were nearly entirely conserved. The amino acid sequences of human alpha and beta subunits were conserved at both Ca(2+)-binding domains. Northern blot analysis of brain RNA showed that human alpha and beta subunit cDNA probes discriminated between alpha and beta subunit mRNAs. By using these subunit-specific cDNA probes, it was demonstrated that alpha and beta subunit mRNAs were expressed in different manners among tumor cell lines: beta was detected in melanoma and some glioma cell lines, while alpha was detected only in a melanoma cell line. Southern blot analysis showed that there were no major deletions and rearrangements of alpha and beta subunit genes in these cell lines, regardless of the level of alpha and beta subunit expression, suggesting that the expression of these subunits may be regulated at the transcriptional or RNA stability level.

Amino Acid Sequence↗

PubMed1992

Conduction velocities of alpha-motor fibers innervating human thenar muscles and order of recruitment upon voluntary contraction.

Conduction velocity (CV) of single alpha-motor fibers was measured using a combination of microneurographic and spike-triggered averaging techniques on 7 healthy subjects (aged 25 to 42). Two tungsten microelectrodes were inserted percutaneously into the median nerve at the wrist and 4 to 6 cm more proximally. Motor unit activities recorded from thenar muscles during voluntary isometric contraction with a third microelectrode, were isolated with a window discriminator, and used to trigger an averager. CVs were calculated by dividing the interelectrode distance by the conduction time between unitary activities in the proximally and distally averaged neurograms. The CVs of 100 units ranged between 34 and 66 m/s, with the peak at around 50 m/s. The relationship between CVs and recruitment orders was compared within sets of 2 or 3 units recorded simultaneously. Statistical analysis using a chi 2 test revealed that slower motor units tended to be recruited earlier than faster units (P less than 0.001).

Action Potentials↗

PubMed1992

Correlation of computed tomography with the histopathology of primary malignant lymphoma of the brain.

The authors present seven autopsy cases of non-AIDS primary malignant lymphoma of the central nervous system to correlate the pathology with the findings of the most recent pre-mortem computed tomogram (CT). Of 10 primary contrast-enhancing (CE) lesions treated by chemotherapy alone, radiotherapy alone, radiochemotherapy, or surgery combined with radiochemotherapy, all but one completely disappeared after the initial course of therapy. However, in six of the seven patients, the final pre-mortem CT demonstrated CE lesions. In three cases CE lesions were at the same site as the primary lesion, in one case in a remote location, and in two cases in diffuse and multiple locations. In all but one case these CE lesions corresponded histologically to tumor nodules or to white matter densely infiltrated by tumor cells. The sole exception was diagnosed pathologically as delayed radiation necrosis. The final CT also showed five low-density areas (LDAs) which had evolved from CE lesions after the completion of therapy. These LDAs corresponded to rarefied or necrotic parenchyma in which tumor cells remained, mainly in the perivascular spaces. One case exhibited diffuse tumor infiltration of periventricular structures which appeared to have normal density and no CE on the final pre-mortem CT.

Aged↗

PubMed1992

Magnetic resonance imaging and histopathology of cerebral gliomas.

The correlation of magnetic resonance imaging (MRI) with histopathological findings was analysed in 26 patients with untreated cerebral gliomas. In low-grade gliomas, T2-weighted images demonstrated relatively homogeneous high-intensity lesions involving both the grey and the white matter. In high-grade gliomas, especially grade IV, T2-weighted images demonstrated prominent heterogeneity in signal intensity, which consisted of a hyperintense "core", less hyperintense or normal intensity "rim" and surrounding finger-like areas of high intensity. Marked and irregular contrast enhancement was evident in all but one case of these high-grade gliomas in which gadolinium-DTPA was used. Histological examination revealed tumour cells extending as far as the borders of the high-intensity areas shown on T2-weighted images in both high- and low-grade gliomas, but in 5 of 8 low-grade and 4 of 18 high-grade gliomas, isolated tumour cells extended beyond the hyperintense areas shown on T2-weighted images.

Adolescent↗

PubMed1992

The presence of 17K Mr protein, a major specific substrate for kinase C, found in the triton-insoluble fraction of synaptosome prepared from rat brain.

Cytoskeletal preparation obtained from synaptosome fractions of rat cerebrum contained the activity of kinase C, which phosphorylated 17K Mr protein endogenous to the preparation. The kinase C activity associated with the synaptosome cytoskeletons is greater in the cerebellum and hippocampus than in the cerebrum. The enhancement rates of phosphorylation of the 17K Mr protein were 293%, 544%, and 526% in the Triton X-100-insoluble fractions of synaptosomes prepared from cerebral cortex, hippocampus, and cerebellum, respectively. The 17K Mr protein was distinct from myelin basic protein (MBP) for the following reasons: 1) The electrophoretic mobility of the protein was slightly smaller than that of major MBP of rat in the polyacrylamide gel of 10-20% linear gradient, and the protein was not contained in the purified rat myelin. 2) The isoelectric point of the protein was in neutral range, whereas that of MBP was in alkaline one. 3) The 17K Mr protein did not cross-react with anti-MBP antibody. The protein was shown to be a major substrate contained in the cytoskeletal preparation of synaptosome obtained from cerebrum except for contaminating MBP. Only serine residue of the 17K Mr protein was phosphorylated by the kinase C endogenous to the preparation. The results suggest strongly that the synaptic role of protein kinase C through phosphorylation of the 17K Mr protein.

Animals↗

PubMed1992

Myocardial Na+,K(+)-ATPase in tachycardia induced cardiomyopathy.

Na+,K(+)-ATPase is a major determinant of myocyte homeostasis and excitation-contraction. Cardiac glycosides such as digitalis and ouabain increase the inotropic state of the heart through the inhibition of Na+,K(+)-ATPase. While cardiac glycosides are commonly used in the setting of congestive heart failure, optimal therapy would depend upon an intact Na+,K(+)-ATPase system. Changes in Na+,K(+)-ATPase activity and glycoside receptor density with the development of cardiomyopathy have not been well defined. Accordingly, left ventricular (LV) function and Na+,K(+)-ATPase activity and glycoside binding were examined in 7 pigs with dilated cardiomyopathy and in 7 controls. Dilated cardiomyopathy was produced by pacing induced supraventricular tachycardia (SVT) for 3 weeks at 240 bpm. Left ventricular function was examined by simultaneous echocardiography and catheterization. Left ventricular fractional shortening significantly decreased with SVT (34 +/- 2 vs. 10 +/- 2%, P less than 0.05) and LV diastolic dimension and pressure significantly increased (3.8 +/- 0.3 vs. 5.1 +/- 0.4 cm, and 8 +/- 2 vs. 27 +/- 2 mmHg, respectively, P less than 0.05) as compared to controls. Na+,K(+)-ATPase activity was assayed as potassium dependent p-nitrophenol-phosphatase activity. Glycoside receptor density (Bmax) and affinity (KD) was determined using [3H]-ouabain binding assays. Na+,K(+)-ATPase activity, Bmax, and KD all significantly fell from control values with SVT induced cardiomyopathy (0.64 +/- 0.06 vs. 0.45 +/- 0.12 micrograms pNP/mg/h, 5.5 +/- 0.4 vs. 1.9 +/- 0.4 pmol/mg, and 15 +/- 3 vs. 9 +/- 3 nM, respectively, P less than 0.05). The distribution of Na+,K(+)-ATPase in LV sections taken from control and SVT hearts were examined using immunohistochemical techniques. A patchy distribution of Na+,K(+)-ATPase along the sarcolemma in SVT sections was observed as opposed to a more uniform distribution in control myocytes. There was no observable change in the relative content and distribution of the Na+,K(+)-ATPase isoforms alpha 2 and alpha 3 in the SVT sections as compared to controls. In an additional set of experiments, changes in LV as well as isolated myocyte responsiveness to ouabain were examined. Left ventricular fractional shortening and peak dP/dt were measured following administration of 20-60 micrograms/Kg of ouabain in control (n = 3) and SVT (n = 3) pigs. In the control group, 40 micrograms/Kg caused a 25% in LV fractional shortening and a 60% increase in peak dP/dt from baseline. Cumulative doses of 60 micrograms/Kg in the control pigs resulted in over a 75% increase in peak dP/dt from baseline values.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

Dissecting aneurysm of the posterior cerebral artery treated with proximal ligation.

A rare case of a dissecting aneurysm of the P3 segment of the right posterior cerebral artery is presented that seems to have occurred in association with mild head injury. The patient was treated surgically because of repeated intramural hemorrhage and enlargement of the aneurysm. Proximal ligation produced thrombosis of the aneurysm without resulting in infarction in the region of the posterior cerebral artery. The mechanisms of the dissection, diagnosis, and treatment are briefly discussed.

Adult↗

PubMed1992

Meningioma in a neonate: case report.

A 10-day-old female with a parasagittal meningioma presenting as a subcutaneous tumor is reported. Meningiomas within the 1st month of life are rare. The clinical and pathological characteristics of congenital meningioma are reviewed.

Female↗

PubMed1992

Interaction of sialosyl cholesterol with the cell surface of rat astrocytes and its biological activities.

The interaction between sialosyl cholesterol (alpha- or beta-D-N-acetyl neuraminyl cholesterol, alpha- or beta-SC) and the plasma membrane of astrocytes was investigated by the use of 14C-labeled alpha- or beta-SC. Both alpha- and beta-SC were dose-dependently and time-dependently bound to rat astrocytes. The Scatchard plot analyses showed that rat astrocytes bound apparently 9.69 x 10(9) molecules of both alpha-SC/cell (apparent Kd = 2.29 x 10(-5) M) and beta-SC/cell (apparent Kd = 5.39 x 10(-5) M) at 37 degrees C. Both the binding of alpha-SC to astrocytes and the subsequent inhibition of DNA synthesis were decreased at the low temperature (4 degrees C), and also suppressed by serum proteins including albumin. One molecule of bovine serum albumin (BSA) bound 2.3 molecules of alpha-SC with the slightly lower Kd-value (8.03 x 10(-6) M) than that for the binding site on astrocytes. BSA not only suppressed the alpha-SC-binding to astrocytes but also increased its release from the cells to the culture media. Gangliosides such as GM1 and GM3 unaffected the alpha-SC-binding, promoted the small release of alpha-SC from the cell surface, and inhibited the morphological changes of astrocytes induced by alpha-SC. The mechanism of alpha-SC-binding to cultured astrocytes with reference to the effects of serum or gangliosides is discussed.

Animals↗

PubMed1992

P400 protein is one of the major substrates for Ca2+/calmodulin-dependent protein kinase II in the postsynaptic density-enriched fraction isolated from rat cerebral cortex, hippocampus and cerebellum.

Concanavalin A-binding glycoprotein with 250 K M(r) found in the postsynaptic density (PSD)-enriched preparation (or synaptic cytoskeleton) from rat cerebellum was identified with P400 protein from the physicochemical properties and enrichment in the cerebellum. Proteins homologous to the cerebellar 250 K M(r) protein occurred in the PSD-enriched preparations from rat cerebral cortex and from hippocampus, although the contents in the preparations were very low. The 250 K M(r) proteins in the PSD-enriched preparations from cerebellum and from cerebrum were highly phosphorylated by Ca2+/calmodulin (CaM)-dependent protein kinase II. The protein of synaptic plasma membrane (SPM) and PSD-enriched fractions prepared from cerebral cortex were not phosphorylated by the cAMP-dependent protein kinase endogenous to the fractions, whereas the protein from cerebellum was done in SPM and PSD-enriched fractions. The facts suggest that P400 or P400-like protein is closely associated with Ca2+/CaM-dependent protein kinase II in the PSD-enriched preparations, especially in the preparation from cerebral cortex. Phosphorylation of the protein by Ca2+/CaM-dependent protein kinase II may play an important role in the postsynaptic function in both cerebellum and at least in some areas of cerebrum.

Animals↗

PubMed1992

Left ventricular volume determined echocardiographically by assuming a constant left ventricular epicardial long-axis/short-axis dimension ratio throughout the cardiac cycle.

OBJECTIVES: The purpose of this study was to develop and test a simplified echocardiographic method to calculate left ventricular volume. BACKGROUND: This method was based on the assumption that the ratio of the left ventricular epicardial long-axis dimension to the epicardial short-axis dimension was constant throughout the cardiac cycle. With use of this constant ratio, the method developed to calculate left ventricular volume at a given point in the cardiac cycle required the left ventricular endocardial long-axis dimension to be measured at only one point in the cardiac cycle. METHODS: Studies were performed in 13 normal dogs, 8 normal puppies, 9 normal pigs, 12 dogs with aortic stenosis, 13 dogs with acute mitral regurgitation, 12 dogs with chronic mitral regurgitation, 7 dogs that had undergone mitral valve replacement and 6 pigs that had had chronic supraventricular tachycardia. Animals with aortic stenosis developed left ventricular pressure overload hypertrophy with a 60% increase in left ventricular mass; chronic mitral regurgitation caused left ventricular volume overload hypertrophy with a 46% increase in left ventricular volume; supraventricular tachycardia caused a dilated cardiomyopathy with a 55% decrease in left ventricular ejection fraction. RESULTS: The left ventricular epicardial long-axis/short-axis dimension ratio remained constant throughout the cardiac cycle in each animal group. End-diastolic and end-systolic volumes calculated with the simplified echocardiographic method correlated closely with angiographically measured volumes; for end-diastolic volume, echocardiographic end-diastolic volume = 1.0 (angiographic end-diastolic volume) -1.8 ml, r = 0.96; for end-systolic volume, echocardiographic end-systolic volume = 0.98 (angiographic end-systolic volume) -0.7 ml, r = 0.95. CONCLUSIONS: Thus the left ventricular epicardial long-axis/short-axis dimension ratio was constant throughout the cardiac cycle in a variety of animal species and age groups and in the presence of cardiac diseases that significantly altered left ventricular geometry and function. The simplified echocardiographic method examined provided an accurate determination of left ventricular volumes.

Animals↗

PubMed1992

Effect of chronic supraventricular tachycardia on left ventricular function and structure in newborn pigs.

OBJECTIVES: The purpose of this study was to examine the effects of supraventricular pacing tachycardia on left ventricular function and myocardial structure in newborn, immature pigs and to determine whether immature pigs respond to supraventricular tachycardia differently from adults. BACKGROUND: Previous studies have shown that supraventricular tachycardia causes dilated cardiomyopathy in adult animals; however, in humans, supraventricular tachycardia-induced congestive heart failure occurs most frequently in children and newborns. Because some clinical diseases may cause myocardial failure in adults but rarely do so in children, it was hypothesized that the effects of supraventricular tachycardia in newborns may be different from those in adults. METHODS: In two groups of newborn swine (3 weeks of age), left ventricular volume, mass and function were assessed with simultaneous echocardiography and cardiac catheterization and myocardial structure was examined with light and electron microscopy. Six piglets underwent 3 weeks of left atrial pacing tachycardia (240 beats/min) and six littermates served as a control group. Both groups were followed up for 3 weeks. RESULTS: At the end of the protocol, left ventricular dimensions increased in the piglets with supraventricular tachycardia compared with values in the control group, but there were no differences in left ventricular mass. Systolic function, assessed by fractional shortening, peak ejection rate and maximal rate of pressure development, was decreased in the group with supraventricular tachycardia. The fractional shortening-end-systolic stress relation in the piglets with supraventricular tachycardia decreased below normal values. Left ventricular diastolic function assessed by the relaxation time constant was prolonged, the peak filling rate was decreased and left ventricular stiffness was increased in the supraventricular tachycardia group. The morphologic data demonstrated that supraventricular tachycardia did not change total myocyte volume but did decrease total myofibrillar volume. CONCLUSIONS: Supraventricular tachycardia caused dilated cardiomyopathy in immature pigs. These changes in left ventricular function were associated with a decrease in cellular contractile proteins. Thus, the effects of supraventricular tachycardia on left ventricular function and structure in immature animals were comparable to previous findings in mature animals.

Age Factors↗

PubMed1992

Facilitation of agonist motoneurons upon initiation of rapid and slow voluntary movements in man.

The time course of facilitation of the agonist motoneurons upon initiation of voluntary ankle dorsiflexion was investigated in eight healthy subjects. The H-reflex and visually guided tracking methods were used for testing the excitability of the motoneuron pool and for controlling the initiation of movement as well as speed and force. Since the onset of voluntary EMG activity (EMG reaction time: EMGvRT) was delayed and/or obscured by test H-reflexes which were evoked very close to the behavioral responses, the subject was instructed to make response movements bilaterally, and EMGvRT was measured on the side without stimulation. In every subject, the EMGvRT was invariably longer in the ramp movement than in the step movement. The onset of H-reflex facilitation prior to EMG onset, which was regarded as indicating the arrival time of the descending motor command to the motoneuron pool, always started earlier in the ramp movement than in the step movement. The difference in facilitation onset between the two tasks was smaller than that in EMGvRT. Since the amplitude of the H-reflex at the onset of the voluntary EMG was equivalent in both movements, the development of H-reflex towards the behavioral EMG onset was more gradual in the ramp movement than in the step movement. The present results demonstrate that the longer reaction time in the slow ramp task depends on 2 factors: delay in the arrival of descending facilitatory impulses to the agonist motoneuron pool, and its slow recruitment thereafter.

Adult↗

PubMed1992

Left ventricular hypertrophy in a canine model of reversible pressure overload.

OBJECTIVE: The goal of therapy for left ventricular pressure overload should include regression of the associated left ventricular hypertrophy, but this process is incompletely understood. The aim of the study was to characterise the extent and time course of the progression and regression of pressure overload left ventricular hypertrophy in a canine hypertrophy model. METHODS: Six puppies were studied longitudinally with haemodynamic and echocardiographic measurements for 10 months. The study animals underwent ascending aortic banding at nine weeks of age which produced an initial gradient of 30 mm Hg. Subsequent growth led to an increase in gradient and the development of left ventricular hypertrophy. Then thoracotomy was again performed to remove the band. One month later, balloon aortoplasty was performed to remove the residual gradient. The animals were then observed for six months. RESULTS: Growth increased the gradient to 105(SEM 10) mm Hg three months after banding. The left ventricular weight to body weight ratio (g.kg-1), an index of hypertrophy, was 7.2(0.5) after three months of pressure overload. Subsequently the band was surgically removed, reducing the gradient to an average of 58(10) mm Hg. Balloon dilatation of the residual aortic stricture reduced the gradient further to 6(5) mm Hg. Over the ensuing six months, echocardiographic determination of left ventricular mass showed the regression in left ventricular hypertrophy. After six months, left ventricular weight to body weight ratio in the previously banded animals was significantly reduced from 7.2(0.5) to 5.3(0.2) (p less than 0.05). CONCLUSIONS: The model produced over 100% left ventricular hypertrophy, most of which regressed following removal of the pressure overload.

Angioplasty, Balloon↗