Cardiomyocyte transplantation does not reverse cardiac remodeling in rats with chronic myocardial infarction

BACKGROUND: Several reports have documented the potential benefits of cell transplantation as an alternative to cardiac transplantation. This study was designed to investigate whether cardiomyocyte transplantation is effective in rats with chronic myocardial infarction. METHODS: Syngeneic Lewis rats were used in this study. Chronic myocardial infarction was induced in rats by ligating the left anterior descending artery. Four weeks later, after left ventricular (LV) dysfunction with akinetic regions was confirmed by echocardiography, the rats were randomized into two groups: a group that received fetal cardiomyocyte transplantation (TX group; n = 11); and a group that received an intramyocardial injection of culture medium only (control group; n = 12). RESULTS: Four weeks after treatment, the TX group had smaller end-systolic dimension (LVDs) (7.5 +/- 0.9 vs 8.9 +/- 0.8 mm, p < 0.01) and better fractional shortening (FS) (26.2 +/- 5.9 vs 17.7% +/- 5.1%, p < 0.01) than the control group. However, there were no differences in LV end-diastolic dimension, LVDs, and FS between baseline and post-treatment values in the TX group. In addition, plasma levels of atrial natriuretic peptide were not significantly different between the two groups 4 weeks after treatment. In microscopic examination, small amounts of transplanted cardiomyocytes were found only in the periinfarct area, not in the center of scar area, and a thicker ventricular wall in the infarct area was detected in the TX group. CONCLUSIONS: Fetal cardiomyocyte transplantation prevented, but did not reverse, cardiac remodeling that was accompanied with heart failure in myocardial infarction rats. Further investigation is warranted for optimal clinical application to the failing heart.     

Composite arterial Y graft has less coronary flow reserve than independent grafts

BACKGROUND: It is not known whether a composite Y graft of the left internal thoracic artery can provide sufficient blood flow to the whole left coronary system. The aim of this study was to compare regional myocardial blood flow (MBF) and coronary flow reserve after coronary artery bypass grafting using arterial composite Y graft or independent arterial grafts. METHODS: Positron emission tomography was performed at rest and after dipyridamole infusion using oxygen-15-labeled water 2 weeks after coronary artery bypass grafting. Regional MBF was calculated in seven segments of the left ventricle. Coronary flow reserve was defined as the ratio of MBF after dipyridamole infusion to MBF at rest. In the Y graft group (n = 22), a free arterial graft to obtuse marginal arteries was anastomosed to the proximal side of in situ left internal thoracic artery, which was anastomosed to the left anterior descending artery. In the independent graft group (n = 13), left anterior descending and obtuse marginal arteries were independently revascularized using in situ left internal thoracic artery and a free arterial graft. RESULTS: There was no difference between the groups in MBF at rest. Coronary flow reserve in the Y graft group was lower than that in the independent group in the anterobasal (1.43 +/- 0.07 versus 1.90 +/- 0.13, p = 0.038), apical (1.24 +/- 0.06 versus 1.64 +/- 0.12, p = 0.003), septal (1.34 +/- 0.05 versus 1.75 +/- 0.13, p = 0.023), and lateral regions (1.19 +/- 0.04 versus 1.66 +/- 0.09, p = 0.001). CONCLUSIONS: Although arterial composite Y graft improved MBF at rest, it was not as effective as independent grafts for improving coronary flow reserve soon after coronary artery bypass grafting.     

Isolation and transplantation of dopaminergic neurons and neural stem cells

Although transplantation of mesencephalic tissue is considered a promising therapy for Parkinson's disease (PD), its clinical use is still restricted to a very few cases. A major limiting factor of this therapy is the difficulty of obtaining sufficient quantities of viable embryonic mesencephalic tissue. To overcome this limitation, techniques to produce dopaminergic (DA) neurons in vitro have been developed. However, these cultures are likely to contain a variety of unidentified cells, which must be removed before implantation. Specific cell-surface markers to sort DA neurons or their precursors are not available. We have developed an alternative strategy, by which these cells can be labeled with green fluorescent protein and isolated with fluorescent activated cell sorter. Transplantation of the sorted cells resulted in recovery of a rat model of the PD. This strategy should be useful for developing new therapies for PD.     

Different blood acetaldehyde concentration following ethanol administration in a newly developed high alcohol preference and low alcohol preference rat model system

A significant difference in blood-acetaldehyde concentration was observed between high alcohol-preference (HAP) rats and low alcohol-preference (LAP) rats, newly developed different alcohol preference lines. This difference of acetaldehyde accumulation may be due to cytosolic aldehyde dehydrogenase (ALDH1) polymorphism, which has been reported previously. As the doses of ethanol we employed are higher than that of voluntary drinking, there may be little direct relationship between acetaldehyde accumulation and alcohol preference. We suggest therefore that the ALDH1 polymorphism is associated with alcohol preference in HAP/LAP lines through some other unidentified mechanism.     

Metastatic urinary bladder tumor from extragonadal germ cell tumor: a case report

A 37-year old male patient complained of lower back pain. Investigations revealed a retroperitoneal tumor and left-sided cervical lymphadenopathy without abnormal findings in both testicles. The diagnosis of extragonadal germ cell tumor was made based on a lymph node biopsy. Following chemotherapy and retroperitoneal lymphoadenectomy, at outpatient follow-up, beta-HCG elevated again. He complained of gross hematuria, cystoscopy showed a bladder tumor, and abdominal MRI scan showed a right ureteral tumor. Total cystectomy and right nephroureterectomy were performed, which revealed that the bladder and ureteral tumors were metastatic germ cell tumors. Six months later, the patient developed hepatic and mesenteric lymph node metastases that failed to respond to treatment, and died. Germ cell tumors metastasizing to the urinary tract are extremely uncommon, and this is the first report of bladder metastases, other than through direct invasion, from an extratesticular germ cell tumor.     

Association between -1438G/A promoter polymorphism in the 5-HT(2A) receptor gene and fluvoxamine response in Japanese patients with major depressive disorder

Genetic polymorphism of the serotonin 5-HT(2A) receptor seems to be associated with therapeutic response to selective serotonin reuptake inhibitors (SSRIs). The present study investigated whether a novel -1438G/A polymorphism in the promoter region of the 5-HT(2A )receptor gene is associated with therapeutic response to fluvoxamine (an SSRI) in 66 Japanese patients with major depressive disorder. Fluvoxamine (50 to 200 mg) was administered twice daily for 6 weeks. Fifty-four patients completed this study. The genotype distribution and the allele frequencies showed no significant difference between responders and non-responders. The time-course of the Montgomery-Asberg Depression Rating Scale scores showed no significant difference among -1438G/G, -1438G/A, and -1438A/A genotype groups. The results demonstrated that the -1438G/A promoter polymorphism in the 5-HT(2A) receptor gene was unlikely to have a major role in therapeutic response to fluvoxamine in Japanese patients with major depressive disorder.     

Questionnaire on the attitude of the physicians in educating the elderly patients with chronic obstructive pulmonary disease about smoking cessation

Smoking status, the extent of recognition of the relationship between smoking and COPD, and actual nature of education for smoking cessation by physicians have not yet been fully elucidated. To investigate perceptions about education for smoking cessation in the elderly by physicians who work in the clinic, questionnaires were sent to the 1,012 physicians who belong to the Yokohama City Medical Association. Of these, 311 respond and their data (31%) were included in the analysis. The questionnaire included questions on the importance of smoking cessation in the elderly, on the perception about the relationship between smoking and various diseases, and actual education for smoking cessation. The smoking status of the physicians themselves was also investigated. The distribution of current smokers, ex-smokers, and non-smokers among the physicians was 13%, 33%, and 54%, respectively. Seventy-five percent of ex-smokers answered that their experience of smoking cessation influenced their patient education for smoking cessation, and 39% of smokers answered that their smoking status did not influence it. Only 53% of the physicians replied that they actually performed education for smoking cessation to the elderly, and 8% of them replied that they hardly perform any or do not perform it. Smoking cessation is thought to be the only way to prevent the development of COPD. However, only a half of physicians recognized the importance of smoking cessation for the treatment and control of COPD in the elderly. In addition, less than one third of physicians perform nicotine replacement therapy for smoking cessation. Enlightenment for physicians should be needed to make them perform education for smoking cessation more aggressively.     

Identification of a novel polymorphism of estrogen receptor-α gene that is associated with calcium excretion in urine

A novel variation of the estrogen receptor-α (ERα) gene was identified by polymerase chain reaction–single-strand conformational polymorphism (PCR-SSCP). It is one base substitution in codon 325 (CCC [allele M] to CCG [allele m]) in exon 4 of the human ERα gene. This substitution did not cause an amino acid change. We categorized 306 unrelated Japanese postmenopausal women into three genotypes: MM, Mm, and mm; the frequency of each genotype was 26.5%, 43.1%, and 30.4%, respectively. Then, the association of this polymorphism with bone mineral density (BMD) of lumbar spine and bone–calcium metabolic markers was studied. There was no significant difference in BMD of the lumbar spine or most of the bone metabolic markers. However, the urinary calcium (Ca) excretion ratio (u-Ca/Cre) corrected by creatinine was significantly lower in the genotype mm group compared with the genotype MM group (MM vs mm, 0.247 ± 0.158 vs 0.200 ± 0.105; P < 0.05). We examined the relationship of restriction fragment length polymorphisms (RFLPs) (PvuII, XbaI) in intron 1 and the polymorphism in exon 4. The frequency of genotype MM was higher in the genotype PPxx, which was reported to be associated with lower BMD in the same population of Japanese postmenopausal women. The ER polymorphism identified in this study might be related to some biological mechanisms that regulate calcium metabolism. Received: Oct. 6, 1997 / Accepted: Sept. 28, 1999     

Enhanced Antitumor Efficacy of a Combination of CPT-11, a New Derivative of Camptothecin, and Cisplatin against Human Lung Tumor Xenografts

The objective of this study was to evaluate the antitumor efficacy of combined use of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carhonyloxycamptothecin (CPT-11) and cisplatin (CDDP). The antitumor activities of CPT-11, CDDP and their combination against 3 human lung tumor xenografts were estimated using congenitally athymic BALB/c ( nu/nu ) mice. The doses were 47 mg/kg for CPT-11 and 6 mg/kg for CDDP on days 1, 5 and 9. In combination therapy, half of the single dosage of each agent was used. The doses were administered intraperitoneally. The antitumor activity and toxicity were evaluated in terms of the tumor volume and body weight change of mice, respectively. The combination therapy resulted in a statistically significant tumor regression compared to the use of only CPT-11 or CDDP in two tumor xenografts out of three. The toxicity of the combination therapy was no higher than that of CPT-11 or CDDP alone. These results suggest that the antitumor activity of the combination of CPT-11 and CDDP is superior to that of CPT-11 or CDDP alone.     

An epidemic of a pertussis-like illness caused by Chlamydia pneumoniae

BACKGROUND: Between June and July, 1994, we encountered an epidemic of a pertussis-like illness in adolescents in a junior high school located in a rural area of Japan. The purposes of this study were to record the clinical manifestations and to identify an etiology. PATIENTS AND METHODS: We interviewed patients and parents and we performed physical examinations on patients with cough during the epidemic. The chest radiographs were also reviewed by us. To identify an etiology we performed culture and serologic studies for a variety of bacteria, Mycoplasma, chlamydiae and viruses. Polymerase chain reaction (PCR) for Chlamydia pneumoniae was carried out on throat swab specimens. RESULTS: Of a total of 230 students 136 (59%) had severe cough illnesses. One developed pneumonia, 9 had bronchitis and the remaining 126 (93%) presented upper respiratory tract infections (URI). The mean duration of cough in cases with URI was 17.4 days and that in cases with bronchitis and pneumonia was 30.4 days. Serology and/or cultures for Bordetella pertussis, Bordetella parapertussis, Mycoplasma pneumoniae, Chlamydia trachomatis, Chlamydia psittaci or viruses were negative. Detection of C. pneumoniae infection was carried out in 46 patients with pneumonia, bronchitis or URI by serology and PCR. The patient with pneumonia, 7 of 7 patients with bronchitis and 32 (84%) of 38 patients with URI were documented to be infected by C. pneumoniae either by serology, PCR or both tests. CONCLUSION: An epidemic of a pertussis-like illness in a junior high school population was caused by C. pneumoniae.