Heterotopic transplantation of the failing rat heart as a model of left ventricular mechanical unloading toward recovery

The left ventricular assist device (LVAD) is usually used in patients with end-stage heart failure as a bridge to transplantation. Recently, some studies have reported functional recovery with the use of an LVAD, although the mechanisms responsible for recovery are not fully understood. We investigated the functional recovery of the infarcted, failing rat heart in response to mechanical unloading after heterotopic transplantation. Heart failure was induced in Lewis rats by ligating the left anterior descending artery. After 4 weeks, the infarcted hearts were harvested and heterotopically transplanted. The transplanted infarcted heart was removed after 2 weeks of unloading and examined for hypertrophy and fibrosis, as well as for mRNA levels encoding for brain natriuretic peptide, sarco(endo)plasmic reticulum Ca(2+)-ATPase2a (SERCA2a), and beta1- and beta2-adrenergic receptors. Normal and infarcted rats without transplantation served as control animals. The infarcted heart was hypertrophied as evidenced by an increase in heart weight and myocyte diameter. After unloading the infarcted heart for 2 weeks, there was a decrease in heart weight and myocyte diameter. However, the percentage of myocardial fibrosis increased after unloading. The mRNA expression of brain natriuretic peptide and the beta2-adrenergic receptor significantly improved after mechanical unloading. The levels of SERCA2a mRNA tended to increase after unloading. In conclusion, unloading the failing, infarcted heart can help normalize left ventricular hypertrophy and cardiac gene expression. This unloading model appears to partially mimic the conditions of hemodynamic support with an LVAD in heart failure patients and potentially offers insights into the mechanisms of functional recovery.     

Education of medical technologists in North America

The increasing complexity of diseases and advancing medical technologies have recently raised the number of test items and their use. This has caused each department to ask for clinical support by medical technologists, including consultation services on clinical laboratory tests in Japan. Under these circumstances, we think it is necessary to consider a Japanese education system for medical technologists to foster people with advanced ability capable in providing adequate clinical support. It is important that we study medical technologist systems and education systems superior to than ours. Therefore, to investigate the state of the Japanese education system for medical technologists, we conducted a comparison between the medical technologist systems and education systems in foreign countries and those of Japan. The social background in which medical technologists are positioned, their scope of work, and the education systems overseas are different from Japan on many points and we were given many suggestions for what a system in Japan should be like.     

EARLY CHANGES IN CEREBRAL ANEURYSMS IN THE INTERNAL CAROTID ARTERY/POSTERIOR COMMUNICATING ARTERY JUNCTION

In order to obtain information about preaneurysmal changes, the junction of the internal carotid artery/posterior communicating artery (ICA/PComA) in the circles of Willis in subjects with aneurysms at sites other than the junction, and in control subjects without aneurysms, were studied by light microscopy.
Small evaginations and thinnings of the media with and without dilatation were observed at the apical areas of the forks with a significantly higher incidence in the aneurysm series than in the control, suggesting some predisposing factor in subjects with aneurysms. As well as funnel-shaped dilatations previously described as the only type of ICA/PComA preaneurysmal change, other more localized types were observed. All the small evaginations and about half of the thinnings and dilatations were observed at the apex in association with a medial gap, but the other half occured at some distance from the apex. The thinned arterial wall showed degenerative changes of the elastic lamina and media. Intimal pads were observed at the apex, the ICA/PComA lateral angle and the ICA stem/branch curve. Their combination with preaneurysmal changes was more frequent in the aneurysm series in comparison with the control.
Degenerative changes of the elastic lamina and media caused by hemodynamic stress due to branching structures including intimal pads are thus presumed to be the initial lesions existing prior to aneurysm formation.     

EFFECTS OF GLUCOCORTICOIDS ON DIFFERENTIATION OF ZONA GLOMERULOSA OF FETAL ADRENAL CORTEX OF RATS

The tissue differentiation of the zona glomerulosa of the fetal adrenal cortex of rats was studied by giving experimental treatments to the fetus in vivo. A low-glucocorticoid-condition was given to the fetus by bilateral adrenalectomy of pregnant rats for removing exogenous glucocorticoids from the fetus, and by brain aspiration of the fetuses for removing the fetal pituitary gland (ACTH) and endogenous glucocorticoids. When the fetus was placed under a low-glucocorticoid-condition for the last couple of days of gestation, poor differentiation of the zona glomerulosa occurred speciflcally in the fetal adrenal cortex. The degree of the poor differentiation seemed to be proportional to the duration of the low-glucocorticoid-condition. Supplemental administration of glucocorticoids could prevent this poor differentiation of the zona glomerulosa. These results indicate that the tissue differentiation of the zona glomerulosa of the fetal adrenal cortex depends much on glucocorticoids.     

Association of natural tooth loss with genetic variation at the human matrix Gla protein locus in elderly women

Natural tooth loss represents a major medical issue within the elderly population, since it impairs masticatory function critical for oral intake of essential nutrition. Contribution of genetic factors has been implicated in the determination of natural tooth loss; degree of reduction in number of natural teeth remaining intact (NTI) varies among individuals; thus, heterogeneity in NTI might reflect genetic variation within the population. One candidate gene, the matrix Gla protein gene (MGP), has been implicated in the pathogenesis of bone loss through a repression of bone/tooth formation. We have investigated a possible association between the CA repeat polymorphism at the human MGP gene locus and the NTI in 458 elderly Japanese women. In 916 chromosomes tested, ten alleles of the polymorphic nucleotide repeat were observed (designated A1–A10), among which five alleles were regarded as major alleles to be tested for the association. Twenty-seven women who possessed an A6 allele (164 bp) had significantly higher NTI than the remaining participants (n=431), who did not carry an allele of that size (mean: 10.0 teeth vs 5.6 teeth; P=0.007, Mann-Whitney test). An eight-year longitudinal follow-up study of NTI suggested that the genetic variations at the MGP locus did not affect the rate of tooth loss in the elderly period. These results suggest that genetic variation at the MGP gene locus is associated with some determinants for tooth loss in elderly women.     

Immunogenic Deposition and Destruction of Glomerulus in IgA Nephritis

The correlation between glomerular immune deposition and histological alteration was studied in serial paraffin sections of kidney biopsy specimens from patients with IgA nephritis using the peroxidase antiperoxidase (PAP) method. IgA deposition was detected in preserved glomerular extracellular matrix or in newly formed interposed matrix along the capillary loops (mesangial interposition). On the other hand, deposition of IgA was scanty or absent in the distorted extracellular matrix where severe exudative inflammation or extracapillary escape of exudates was occurring segmentally. Ultrastructurally such extracellular matricial destruction was expressed as splitting or thinning of the lamina densa, as well as mesangial edema, reticulation or mesangiolysis of the axial matrix. Therefore it appears that at least two types of change in the extracellular matrix are induced by IgA immune complexes in IgA nephritis; immunogenic deposition and destruction.     

Polyarteritis Nodosa with Atrophy of the Left Hepatic Lobe

A 73-year-old Japanese man with a history of partial gastrectomy due to gastric cancer 4 years previously was admitted because of intermittent fever. The patient developed abdominal pain, erythema, and myalgia in addition to the fever during the final clinical course, and died of acute heart failure. Autopsy disclosed atrophy of the left lobe of the liver and acute myocardial infarction. Neither metastasis nor recurrence of the cancer was observed. Small and medium-sized arteries of the visceral organs showed various stages of necrotizing vasculitis with narrowing of the lumina. The vasculitis was most prominent in the left lobe of the liver and in the heart. Narrowing of the portal vein due to portal tract inflammation in addition to vasculitis of the hepatic arteries may have induced ischemia and infarction, which had resulted in atrophy of the left hepatic lobe. Acta Pathol Jpn 42: 662–666, 1992.     

Effect of cyclooxygenase inhibitor on excessive sputum

Indomethacin suppository and aspirin inhalation reduced the amounts of sputum in the patients with bronchiectasis and chronic bronchitis. A 67-year-old woman with bronchiectasis received indomethacin suppository to relieve the lumbar pain. After the start of indomethacin, a reduction in the amount of sputum was observed and the volume of sputum returned to pretreatment levels after the cessation of indomethacin. Levels of cyclooxygenase products in the sputum during indomethacin was also much lower than their levels after discontinuance of indomethacin. A 64-year-old man with chronic bronchitis was also administered inhaled aspirin to control the sputum volume. Both indomethacin suppository and aspirin inhalation reduced the amounts of sputum. In addition to these cases, a 31-year-old woman with bronchial asthma was tried to control the sputum production with indomethacin, but it had no effect on the sputum volume. It is suggested that these drugs may be useful in the treatment of excessive sputum in bronchiectasis and chronic bronchitis.     

The properties of the Kir6.1–6.2 tandem channel co-expressed with SUR2A

Functional ATP-sensitive K (KATP) channels have an octameric subunit structure with four pore-forming subunits (Kir6.x) and four sulfonylurea receptors (SURx). In the present study, the properties of the heteromeric KATP channel whose pore subunits are composed of Kir6.1 and Kir6.2 were examined using a heterologous expression system. In COS7 cells co-transfected with Kir6.1, Kir6.2 and SUR2A at a ratio of 1:1:2, KATP channels showed various unitary conductances between those of Kir6.1/SUR2A (33.6+/-4.2 pS) and Kir6.2/ SUR2A (67.1+/-1.6 pS). Kir6.1-6.2 tandem protein, constructed by fusing the C-terminus of Kir6.1 to the N-terminus of Kir6.2 with a ten glutamine linker sequence, also formed a channel with an intermediate conductance (58.9+/-1.5 pS). Kir6.2 and Kir6.1-6.2 showed similar sensitivity to ATP4-: half-maximal inhibition (IC50) was obtained at 14.1+/-12.8 microM and 17.6+/-9.6 microM, respectively. In the presence of Mg2+, Kir6. 1-6.2 was significantly less sensitive than Kir6.2 to MgATP (IC50=95.5+/-49.6 microM versus 18.9+/-5.0 microM). These results suggest that Kir6.1 and Kir6.2 are endowed with the potential to form a heteromeric KATP channel, which has a low sensitivity to MgATP.