Nakaaki Ohsawa

Coronary angioplasty of chronic total occlusions with bridging collateral vessels: immediate and follow-up outcome from a large single-center experience.

OBJECTIVES The purpose of the present study was to assess the effect of bridging collateral vessels on the success of coronary angioplasty of chronic total occlusions in the context of state of the art technology and operator skill. BACKGROUND Coronary angioplasty of chronic total occlusions has been associated with relatively low success rates. Because the presence of bridging collateral vessels in chronic total occlusion has been reported to be the major predictive factor in procedural failure, angioplasty is often not recommended in patients with such vessels. METHODS Three hundred ninety-seven consecutive patients undergoing coronary angioplasty for chronic total occlusion were classified into two groups. Patients in group I had chronic total occlusion with bridging collateral vessels (97 patients, 109 total occlusions), and patients in group II had chronic total occlusion without such vessels (300 patients, 324 total occlusions). RESULTS The mean +/- SD duration of occlusion was 46 +/- 66 months (range 2 to 170) in group I and 27 +/- 39 months (range 2 to 112) in group II (p < 0.05, high power value 0.83, group I vs. group II). Angioplasty for single-vessel disease was performed in a smaller proportion of patients in group I than in group II (22% vs. 36%, p < 0.05; power value 0.77). Procedural success was achieved in 82 chronic total occlusions in group I and 270 chronic total occlusions in group II (75% vs. 83%, p = 0.07; power value 0.53). The rates of restenosis and reocclusion were 54% and 16%, respectively, for group I and 56% and 13%, respectively, for group II (p = 0.76, 0.46; power value 0.51, 0.47). Complications were minor with no Q wave infarction or requirement for urgent bypass surgery in either group. Of 81 patients with unsuccessful coronary angioplasty, 1 patient from group I (1%) and 3 patients from group II (1%) required pericardiocentesis because of cardiac tamponade. Guide wire manipulation did not impair the flow of bridging collateral channels in group I. CONCLUSIONS Coronary angioplasty can open chronic total occlusions, with or without bridging collateral channels, for safe and effective recanalization without major complications.

Activation of lavage lymphocytes in lung injuries caused by radiotherapy for lung cancer

PURPOSE Radiation pneumonitis sometimes extends beyond the irradiated area of a lung and can also affect the opposite lung. Some immunological mechanisms, in addition to simple direct injury of the lungs by radiation, seem to be involved in the onset of radiation pneumonitis. To clarify such mechanisms, the effects of radiation on local inflammatory cells in lungs, in particular, lymphocytes, were examined. METHODS AND MATERIALS A comparison was made of bronchoalveolar lavage fluid (BALF) findings from 13 irradiated patients (RT group) and 15 nonirradiated patients (non-RT group) with lung cancer. Patients who later developed radiation pneumonitis (RP group) and those who did not (RP-free group) were also compared. Using a two-color flowcytometer, radiation-induced changes in local inflammatory cells in lungs were analyzed. This included analyses of human leukocyte-associated antigen (HLADR) and intercellular adhesion molecule-1 (ICAM-1) expression on T-cells, which are though to be involved in cell activation and interactions between cells. RESULTS The following aspects of BALF were higher in the RT group than in the non-RT group: (a) the percentage of lymphocytes and eosinophiles; (b) the incidence of HLADR-positive CD4+T-cells and HLADR-positive CD8+T-cells; and (c) the incidence of ICAM-1--positive T-cells. The following aspects of BALF were higher in the RP group than in the RP-free group: (a) the total cell counts; (b) the percentage of lymphocytes; and (c) the incidence of ICAM-1-positive T-cells. A significant relationship was seen between the incidence of ICAM-1 expression on T-cells and the number of days from the initiation of radiotherapy to the onset of radiation pneumonitis. CONCLUSION These data suggest that irradiation can induce accumulation of activated T-cells (HLADR and ICAM-1--positive T-cells) in the lung. This accumulation may be closely linked to radiation-induced lung injury. It is also suggested that the incidence of ICAM-1--positive T-cells in BALF may serve as a useful clinical marker of radiation pneumonitis.

Expression of α and β genes of human chorionic gonadotropin in lung cancer

To confirm the ectopic production of human chorionic gonadotropin (hCG) in lung cancer, we attempted to detect the presence of mRNA transcripts of the α and β genes for hCG in lung cancer tissues obtained from surgical operations. Although we were able to show the presence of hCGβ mRNA transcripts in lung cancer tissue by Northern blot, the sensitivity of the assay was too low for a precise analysis of hCGB mRNA transcripts in most lung cancers. Using reverse transcription PCR (RT‐PCR) and Southern blot analysis, however, various amounts of mRNA transcripts of hCGβ genes 3, 5, 7 and 8 were demonstrated in 9 of the 14 lung cancer tissues examined, while no mRNA transcripts were detectable in 12 normal lung tissues from the same patients. Our results are consistent with a clear difference in serum and urinary hCGβ levels observed between normal subjects and lung cancer patients. The expression of the hCGα gene, however, was detected in normal lung tissues more frequently than in lung cancer tissues using RT‐PCR Southern blot. Our results strongly suggests the production of hCGβ as being part of the phenotype of malignantly transformed lung cells and further strengthen its superior specificity over intact hCG or hCGα as a tumor marker for lung cancers. Int. J. Cancer 71:539‐544, 1997.

Herpes simplex Virus Myelitis: Clinical Manifestations and Diagnosis by the Polymerase Chain Reaction Method

Herpes simplex virus (HSV) myelitis has previously been reported to be a form of acute ascending necrotizing myelitis caused by HSV type 2 (HSV-2). We studied neurological symptoms, clinical course, magnetic resonance imaging (MRI) findings, and diagnosis by polymerase chain reaction (PCR) methods in 9 patients with HSV myelitis. In 6 cases, disease onset was marked by sensorimotor disturbances of lower extremities and urinary disturbances, with the transverse myelopathy gradually ascending to the cervicothoracic spinal cord level. The other 3 cases showed transverse myelopathy without an ascending pattern. Six cases showed acute progression, while 3 cases showed a subacute course. There were 2 cases with recurrent episodes. Three patients recovered, however, in the remaining 6 patients severe sequelae such as paraplegia persisted despite antiviral therapy. MRI showed a hyperintense lesion on T2-weighted images. Gadolinium enhancement was observed in 2 cases, and 1 case showed a hyperintense lesion both on T1- and on T2-weighted images, suggesting hemorrhagic necrosis. HSV-2 was detected by PCR techniques in all 6 cases with an ascending pattern. HSV-1 DNA was detected in 2 and HSV-2 DNA in 1 of the 3 cases with a nonascending pattern. Our findings demonstrate diverse clinical manifestations of HSV myelitis.

Inhibition of smooth muscle cell migration by the p21 cyclin-dependent kinase inhibitor (Cip1)

In vascular smooth muscle cells (SMCs), proliferation and migration contribute to lesion formation after arterial injury. In the cell cycle, several cyclin-dependent kinases (cdks) inhibitors are implicated in the regulating of cyclin-cdk activity such as p21Cip1, p16Ink4 and p27Kip1. Although Cip1 inhibits SMC proliferation, its effects on SMC migration are unknown. To test the hypothesis that Cip1 inhibits SMCs migration and proliferation, we transfected the Cip1 gene into a strain of rabbit aortic SMCs (SM3 cells). Both the spreading and the attachment of Cip1-transfected SM3 cells to extracellular matrices (ECMs) were inhibited compared to that of vector-transfected cells. In the modified Boydens chamber assay the effect of fibronectin on the migratory activity of Cip1-transfected SM3 cells was significantly less than that of vector transfected cells in response to PDGF-BB. These data suggested that Cip1 inhibited both the migration and proliferation of SMC.

Hypoparathyroidism and insulin‐dependent diabetes mellitus in a patient with Kearns–Sayre syndrome harbouring a mitochondrial DNA deletion

We report a 17‐year‐old girl with short stature, external ophthalmoplegia, atypical retinal pigmentary degeneration, sensorineural hearing loss, and cardiac conduction defect (Kearns–Sayre syndrome). A large‐scale deletion (6741 base pairs) in mitochondrial DNA was found in her muscle specimen. She also had insulin‐dependent diabetes mellitus (IDDM). On admission, her plasma glucose level was elevated at 31.0mmol/l with mild ketoacidosis, and haemoglobinA1c elevated at 16.5%. After improvement of diabetic ketoacidosis, she was placed on insulin 24–30 units/day despite her small body weight of 25 kg. There was reduced excretion of urinary C‐peptide at 3.97 nmol/day. In addition, she had idiopathic hypoparathyroidism with a serum calcium level of 2.15 mmol/l, phosphate 1.7 mmol/l, and intact PTH below 10 ng/l. Human leucocyte associated antigen typing showed A24, A26; B54, B61; CW1, CW3; DR8, DR14; DQ1 and DQ3, suggesting that the presence of HLA‐A24 and CW3 antigen contributed to the association of IDDM and hypoparathyroidism, similar to Japanese patients with polyglandular autoimmune syndrome, complicated by hypoparathyroidism and IDDM. We suggest that a genetic linkage, as well as mitochondrial dysfunction, may be responsible for the association of the two disease states. This is an extremely rare case of Kearns–Sayre syndrome, presenting in association with IDDM and idiopathic hypoparathyroidism.

Transcriptional activation by the androgen receptor in X-linked spinal and bulbar muscular atrophy

Polyglutamine tracts encoded by trinucleotide CAG repeats have been found in some transcription factors. Expansion of the polyglutamine tracts in the androgen receptor (AR) has been recognized as a cause of X-linked spinal and bulbar muscular atrophy (SBMA). To study the role of AR as a transcription factor in SBMA, we constructed AR genes encoding expanded polyglutamine tracts (repeat numbers = 52, 92, 132, and 212), and analyzed AR-induced transcriptional activation in NG108-15 cells. We found that AR-induced transcriptional activation gradually decreased with increasing glutamine repeat numbers, and polyglutamine expansion caused a specific reduction in transcription activity in motor neurons. However, the degree of reduction was slight in comparison with the normal AR gene and that of SBMA. Thus, subtle disorders of transcriptional control may occur in SBMA.

Postprandial hypotension in patients with non-insulin-dependent diabetes mellitus

This study attempted to determine whether postprandial hypotension (PPH) is associated with diabetes mellitus by 24-h ambulatory blood pressure monitoring (24-h ABPM) and by monitoring blood pressure during 75-g oral glucose tolerance test (75-g OGTT) in 15 normal subjects and 35 patients with non-insulin-dependent diabetes mellitus. When we defined PPH as a postprandial decrease in systolic blood pressure of greater than 20 mmHg, the incidence of PPH in diabetics was 37% by 24-h ABPM and 20% by 75-g OGTT. The incidence of proliferative retinopathy and proteinuria was greater in diabetics with PPH than in those without PPH. All of the patients with PPH had somatic and autonomic neuropathy. The C-peptide response was lower in diabetics with PPH than in those without PPH. We revealed the presence of PPH in diabetics, and found that PPH was closely related to disease severity, especially diabetic autonomic neuropathy.

Acarbose improved severe postprandial hypotension in a patient with diabetes mellitus.

Postprandial hypotension (PPH) is defined as a decrease of systolic blood pressure by more than 20 mmHg after meals. Severe PPH is a troublesome diabetic complication, which has no established means of treatment. We encountered a patient who had diabetes mellitus complicated by severe PPH and attempted to treat this problem using several medications (octreotide, midodrine hydrochloride, and acarbose). A 58-year-old male with diabetic triopathy complained of orthostatic dizziness and vertigo after meals. The blood pressure was monitored for 24 h with an ambulatory blood pressure monitor, revealing that the systolic blood pressure decreased markedly after breakfast and dinner by 45 and 50 mmHg, respectively. PPH was not improved by a subcutaneous injection of octreotide. Administration of midodrine hydrochloride reduced the frequency of hypotensive episodes from twice to once daily, but the magnitude of the postprandial fall in blood pressure was still around 30 mmHg. After the patient started to receive acarbose therapy, the postprandial fall in blood pressure was diminished to 18 mmHg and his symptoms largely disappeared. For the treatment of PPH in diabetic patients, our experience suggests that it may be appropriate to try first on alpha-glucosidase inhibitor like acarbose.

Inhibition of migration and proliferation of vascular smooth muscle cells by dehydroepiandrosterone sulfate

Dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) are the most abundant steroids in humans, and their serum concentrations progressively decrease with age. Although relationships between DHEA(-S) and many age-related illnesses have been postulated, the mechanisms for their effects remain unknown, and specific receptors for these molecules have not been identified. In this paper, to investigate the role of DHEA(-S) in atherogenesis, we studied the proliferation and migration of a rabbit vascular smooth muscle cell line, SM-3, in the presence of DHEA(-S). Cellular proliferation was inhibited by DHEA-S, and to a lesser extent by DHEA. Modified Boydens chamber assays revealed that DHEA-S inhibited the migration of SM-3 cells toward PDGF-BB. In cell attachment assays, DHEA-S inhibited the attachment of SM3 cells to fibronectin. It was suggested that the inhibitory effect of DHEA-S for SM-3 proliferation and migration was due to the decreased interaction with fibronectin. Scatchard analysis revealed the presence of two populations of DHEA-S binding sites in the nuclear fraction, and a smaller number in the cytosolic fraction. Since the dissociation constant of the higher affinity site was similar to the serum DHEA-S concentration in humans (Kd = 5.8 microM), this binding site could be functional under physiologic conditions. These findings suggest that there may be receptor-mediated anti-atherogenic actions of DHEA-S.