[Ganglioneuroma detected in a patient over age 60].

We report a case of ganglioneuroma in a 67-year-old woman who presented with an abnormal shadow at a medical examination. She was admitted and chest radiography disclosed a mass in the upper right mediastinum. We suspected a mediastinal tumor after chest CT, chest MRI and bronchofiberscopic examination, and so surgical treatment was performed. The histopathological diagnosis was ganglioneuroma. Ganglioneuroma is thought of as a children's disease and adult onset is rare. We reasoned that ganglioneuroma should be included among the mediastinal tumors in patients over 60.

[Results of questionnaire on open disclosure to patients with malignant lung tumors comparison of responses before and after chemotherapy].

To investigate patient attitudes towards open disclosure of malignant disease, we conducted a questionnaire survey of 17 patients with malignant lung tumors, to whom the nature of their disease was revealed. The questionnaire used a 100 mm analog scale. Ten of the patients were treated by chemotherapy and their questionnaire results before and after treatment were compared. It was found that they were mostly satisfied about being truthfully informed and that, indeed, they were anxious to know their true diagnoses. They were also keen to have their true prognosis revealed, but not as much as the diagnosis. They also wished to be informed about treatment and its effects. These attitudes showed no marked changes resulting from the administration of chemotherapy, and we therefore concluded that chemotherapy itself had no influence on patients' feelings about disclosure. The questionnaire was well accepted and was useful in judging attitudes to open disclosure.

[Lung cancer detected in a patient under age 40 treated for pneumothorax].

We report a case of lung cancer in a relatively young patient who presented pneumothorax. A 31-year-old man complaining of pressure in his left chest was admitted with left pneumothorax disclosed on X-ray film. Although pleural drainage was performed for a week, the left lung did not expand well, and surgical treatment was required. During surgery, a tumor (1.5 x 1.0 cm in size) was discovered in the upper lobe of the left lung (S3). Histopathological examination revealed that it was a large cell carcinoma. People under the age of 40 account for only a small fraction of the entire lung cancer patient population. Pneumothorax occurs together with lung cancer, especially in people under age 40. We reasoned that lung cancer should be considered a possible complication in patients under 40 who experience recurrent or prolonged bouts of pneumothorax.

A case of malignant lymphoma with diastolic heart failure.

In patients with malignant lymphoma, the first signs and symptoms are frequently noncardiac and clinical manifestations of cardiac involvement are often nonspecific. This case report presents a patient with malignant lymphoma whose first manifestation was characteristic of heart failure, mainly due to diastolic dysfunction, and whose postmortem examination revealed massive myocardial invasion.

The terminal protein of the linear DNA plasmid pGKL2 shares an N-terminal domain of the plasmid-encoded DNA polymerase.

The 36K protein attached at the 5' end of the linear DNA plasmid pGKL2 from the yeast Kluyveromyces lactis was first purified and characterized. The terminal protein was purified from cells (1 kg wet weight) by ammonium sulphate precipitation and two rounds of centrifugation to equilibrium in CsCl gradients. The pGKL2 was present only in the post-microsomal supernatant. Approximately 10 mg of the purified pGKL2 was recovered and digested with DNase I. The terminal protein (final ca. 0 center dot 8 mg) was homogeneous by electrophoresis and we determined the N-terminal amino acid sequence up to ten residues, showing that it existed in the cryptic N-terminal domain of pGKL2-ORF2 (DNA polymerase) sequence.

Altered cardiovascular responses to purinergic A2 stimulation in the nucleus tractus solitarius of spontaneously hypertensive rats.

OBJECTIVE: To investigate the cardiovascular effects of adenosine A2 receptor stimulation in the nucleus tractus solitarius and whether these effects are altered in hypertension. DESIGN AND METHODS: Ten- or 11-week-old spontaneously hypertensive rats (SHR) or Wistar-Kyoto (WKY) rats were anaesthetized with urethane. Adenosine (100 ng) or adenosine A2 agonist (2-octynyladenosine, 5 ng) were micro-injected (50 nl) into the nucleus tractus solitarius. Blood pressure and heart rate were measured from a femoral artery. Sympathetic nerve activity was recorded from the abdominal splanchnic nerve. RESULTS: Blood pressure, heart rate and sympathetic nerve activity were consistently decreased after the micro-injection of adenosine into normotensive rats. Changes from the baseline in blood pressure, heart rate and sympathetic nerve activity were significantly smaller in SHR than in WKY rats (blood pressure: SHR -5.6 +/- 2.1% versus WKY rats -20.0 +/- 2.1%; heart rate: SHR -5.4 +/- 0.88% versus WKY rats -9.2 +/- 2.3%; sympathetic nerve activity: SHR -5.5 +/- 1.1% versus WKY rats -21 +/- 2.8%). Micro-injection of an A2 agonist into the nucleus tractus solitarius also decreased blood pressure and heart rate, and those responses were not inhibited by pretreatment with an adenosine A1-specific antagonist. The response induced by micro-injection of A2 agonist into the nucleus tractus solitarius was significantly smaller in SHR than in WKY rats, whereas the changes in heart rate did not differ statistically (blood pressure: -23.4 +/- 4.7% versus -10.8 +/- 2.1%; heart rate: -12.1 +/- 1.2% versus -13.6 +/- 2.1%). CONCLUSION: The present results suggest that stimulation of adenosine A2 receptors in the nucleus tractus solitarius decreases both blood pressure and inhibitory sympathetic nerve activity and that those inhibitory responses to adenosine in the nucleus tractus solitarius are deranged in SHR.

Association of blood pressure variability with induction of atherosclerosis in cholesterol-fed rats.

The influence of increased lability of blood pressure on the development of aortic atherosclerosis was examined. Because sinoaortic denervation (SAD) produced increased lability of blood pressure without blood pressure elevation, the development of atheromatous plaque was examined in SAD rats. These rats were fed a high-cholesterol diet and were denuded of endothelium so that development of atherosclerosis was accelerated. Five groups of male Wistar rats were used: A) controls, B) high-cholesterol diet (HC), C) HC+denudation (DN), D) HC+DN+renal artery clipping (2K1C), and E) HC+DN+sinoaortic denervation (SAD). Denudation was accomplished by scraping the aortic lumen with a balloon catheter, and hypertension was induced by clipping the left renal artery. After recording blood pressure and heart rate for 6 weeks, the rats were killed, blood samples were collected, and thoracic aortas were removed for pathologic examination. All the groups of rats fed a high-cholesterol diet developed marked hypercholesterolemia and hypotriglyceridemia. High-cholesterol diet alone could not induce aortic atherosclerosis, whereas aorta of HC+DN rats showed slight intimal thickening with smooth muscle cell proliferation. On the other hand, aorta of HC+DN + 2K1C rats showed marked atheromatous plaque with prominent cellular proliferation, and aorta of SAD rats also showed mild to moderate atheromatous plaque. Accordingly, we concluded that increased variability in circadian blood pressure per se, as well as hypertension, could induce aortic atherosclerosis in the hypercholesterolemic and endothelium-denuded rats.

Alteration of response to neuropeptide Y in the nucleus tractus solitarius of spontaneously hypertensive rats.

In normotensive rats, microinjections of neuropeptide Y (2.5 to 25 pmol) into the unilateral nucleus tractus solitarius elicited dose-dependent vasodepressor and bradycardiac responses accompanied by an inhibition of sympathetic nerve firing. After microinjections of the alpha 2-adrenergic receptor antagonist yohimbine (100 ng) into the nucleus tractus solitarius, the depressor and bradycardic responses to the injection of neuropeptide Y (25 pmol) into the nucleus tractus solitarius were significantly attenuated. In contrast, pretreatment with the alpha 1-adrenergic receptor antagonist doxazosin (200 ng) injected into the nucleus tractus solitarius did not alter these responses. In spontaneously hypertensive rats, microinjections of neuropeptide Y (25 pmol) into the nucleus tractus solitarius also elicited depressor and bradycardic responses that were significantly less than those of normotensive Wistar-Kyoto rats. However, pretreatment with yohimbine (100 ng) in the nucleus tractus solitarius did not diminish these depressor responses in spontaneously hypertensive rats. Depressor responses to neuropeptide Y, which was administered after yohimbine pretreatment, were also less in Wistar-Kyoto rats than in spontaneously hypertensive rats. The results suggest that the depressor and bradycardic responses elicited by neuropeptide Y were accompanied by the inhibition of sympathetic nerve activity. These responses may be mediated in part by alpha 2-adrenergic receptor in the nucleus tractus solitarius. The impairment of alpha 2-adrenergic receptor-mediated responses to neuropeptide Y in spontaneously hypertensive rats may contribute to the development of hypertension.

Clonidine improves central attenuation of the baroreflex in spontaneously hypertensive rats.

To determine whether clonidine can improve the central alteration of the baroreflex in SHR, the centrally cut end of the aortic depressor nerve was electrically stimulated in SHR with intravenously administered clonidine. Aortic depressor nerve (ADN) stimulation elicited depressor and sympatho-inhibitory responses in a frequency-dependent manner in WKY and SHR. These responses were significantly smaller in SHR than in WKY. The attenuated depressor and sympatho-inhibitory responses to ADN stimulation in SHR were restored following i.v. injections of clonidine, although the drug did not affect the responses to ADN stimulations in WKY. These findings suggest that clonidine can improve central attenuation of the baroreflex in hypertension.

Role of sympathetic nerve inhibition in the vasodepressor effect of bromocriptine in normotensive and hypertensive rats.

This study aimed to elucidate the mechanism of the hypotensive effect of bromocriptine (BRC), and to investigate whether or not the effects of BRC on the sympathetic nervous system are altered in hypertension. BRC was administered intravenously to normotensive and spontaneously hypertensive rats (SHR). It elicited hypotensive effects dose-dependently in urethane-anaesthetized normotensive rats, an effect which was antagonized with metoclopramide. Pretreatment with intravenous hexamethonium attenuated the hypotensive effect of BRC. BRC decreased plasma norepinephrine (NE) without inhibiting the sympathetic nerve spikes recorded from the postganglionic sympathetic nerve bundle. The hypotensive effect of BRC was significantly greater in SHR than in Wistar Kyoto Rats (WKY). Decrease in NE by BRC was also significantly greater in SHR than in WKY. These results suggest that the hypotensive effect of BRC is induced by suppression of NE release, not by inhibition of sympathetic nerve spikes, and that the dopaminergic presynaptic inhibition is attenuated in SHR.

Decreased hypothalamic and medullary GABA turnover in spontaneously hypertensive rats.

OBJECTIVE: The aim was to assess whether Gamma-aminobutyric acid (GABA) neurone activities in the central nervous system, especially in the hypothalamus and medulla oblangata, are altered in hypertension. METHODS: Central GABA content and turnover rate were measured in spontaneously hypertensive rats (SHR) and their normotensive Wistar Kyoto controls (WKY). GABA content was determined with high performance liquid chromatography, and in vivo GABA turnover rates were estimated by GABA accumulation after injection of amino-oxyacetic acid, a selective inhibitor of GABA degrading system. Two groups of nine week old male rats (32 SHR and 32 WKY) were used. RESULTS: GABA concentrations in cerebrospinal fluid were lower in SHR than in WKY. Since hypothalamus and medulla oblongata are the possible active sites of this system, basal GABA contents and in vivo GABA turnover rates were measured in hypothalamus and medulla oblongata. Basal GABA content in the medulla oblongata and hypothalamus was almost equal in SHR and WKY. On the other hand, GABA turnover rates were significantly lower in SHR than in WKY in both the hypothalamus and the medulla. CONCLUSIONS: Since it is known that GABA is an inhibitory neurotransmitter in the central nervous system and that it controls autonomic and cardiovascular activities, the findings suggest that the decreased hypothalamic and medullary GABAergic activities may permit sympathetic hyperactivity to contribute to the increase in blood pressure in SHR.

Manidipine inhibits the progression of hypertension and atherosclerosis in endothelium-injured and cholesterol-fed Goldblatt 2K1C rats.

In the present study, arteriosclerotic change of the aorta was induced in rats. The effects of manidipine hydrochloride on the resulting hypertension and arteriosclerotic change were studied. In endothelium-injured cholesterol-fed Goldblatt 2K1C rats, moderate elevation of blood pressure was noted at 3, 4, and 5 weeks. Laboratory studies performed at the end of 6 weeks also showed hypercholesterolemia, accompanied by a reduction of triglycerides and HDL cholesterol. Regular doses of manidipine (200 or 500 mg/kg) resulted in a dose dependent inhibition of the blood pressure elevation and a reduction of HDL cholesterol, but had no effect on cholesterol or triglyceride levels. Morphological studies in endothelium-injured rats afflicted with hypercholesterolemia and hypertension, showed medial thickening and intimal hyperplasia. Hyperplasia of the intima was a result of excessive proliferation of the smooth muscle cells. These cells showed an unusually large number of fat droplets and were considered indicative of atheromatous plaque formation. In rats treated with manidipine, hyperplasia of the media was completely suppressed while hyperplasia of the intima was reduced by a minimum of 50%. This study demonstrated that hypercholesterolemia and hypertension produced arteriosclerotic change in endothelium-injured rats, which was inhibited by manidipine. It is not known whether antiarteriosclerotic action was involved in the antihypertensive effect of manidipine.

Effect of manidipine on cardiac hypertrophy and coronary circulation in DOCA/salt hypertensive rats.

The effect of manidipine on cardiac hypertrophy, coronary circulation, left ventricular weight and maximal coronary flow in hypertension was measured in DOCA/salt treated systolic hypertensive rats with and without manidipine treatment. Normotensive rats were used as controls. After feeding with 0.05% manidipine-containing food, blood pressure was reduced only in DOCA/salt hypertensive rats, but not in control rats. After 3 weeks of treatment, sodium excretion was significantly increased in DOCA/salt-treated rats with or without manidipine treatment. Hearts were removed and perfused with modified Krebs-Henseleit solution with adenosine (5 x 10(-5) M) in a Langendorff apparatus. Maximal coronary flow (MCF) was significantly decreased only in DOCA/salt hypertensive rats without treatment, while manidipine treatment restored MCF. Left ventricular weight/body weight was also markedly greater in DOCA/salt-treated rats not given manidipine. Left ventricular weight in DOCA/salt-treated rats given manidipine was significantly reduced compared with DOCA/salt hypertensive rats without treatment, although it was heavier than in the control animals. Morphological examination showed that the increased wall/lumen ratio in DOCA/salt hypertensive rats was reduced by manidipine treatment. These findings suggest that treatment with manidipine in DOCA/salt hypertensive rats lowered high blood pressure and improved impaired coronary circulation with a reduction in left ventricular and vascular hypertrophy.

Altered noradrenergic projection to hypothalamus via baroreflex in spontaneously hypertensive rats.

To determine whether noradrenergic projections to the posterior hypothalamus via baroreflex are altered in the hypertensive state, the extracellular norepinephrine (NE) content of the posterior hypothalamus was measured in both spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) after sinoaortic denervation (SAD) or sham operation. In WKY, blood pressure (BP) and extracellular NE content 24 h after SAD were significantly higher than those of sham-operated rats. Contrarily, SAD did not increase both BP and NE in the posterior hypothalamus of SHR. These results suggest that the noradrenergic pathway via the baroreflex is impaired in SHR. This mechanism may play an important role in the development and maintenance of hypertension in SHR.

Sympathetic inhibition and attenuation of spontaneous hypertension by PVN lesions in rats.

To determine whether the paraventricular nucleus (PVN) contributes to the development of hypertension in spontaneously hypertensive rats (SHR), we compared cardiovascular responses to ganglionic blockade with hexamethonium or vasopressin antagonism with dPVAVP in sham-operated or PVN lesioned SHR and Wistar-Kyoto rats (WKY). Lesions were produced electrolytically when the rats were 5 weeks old. During the next 3 weeks, tail-cuff measurements showed that the development of hypertension in SHR was inhibited, while systolic pressure in WKY was unaffected. Mean pressures recorded directly from the femoral artery at 8 weeks of age were lower in lesioned than in sham-operated SHR (141 +/- 5 vs 110 +/- 3 mm Hg, P less than 0.05), but did not differ in corresponding WKY groups (110 +/- 4 vs 112 +/- 5 mm Hg). Depressor responses to ganglionic blockade induced by i.v. injection of hexamethonium (25 mg/kg) were significantly larger in sham-operated than in lesioned SHR (-41 +/- 4% vs -28 +/- 3%, P less than 0.05). By contrast, vasopressin antagonism with dPVAVP did not alter blood pressure in all rat groups. In 24-h urine samples, excretion of vasopressin was unaffected, but that of norepinephrine was significantly reduced in lesioned SHR. These findings suggest that the PVN contributes to the development of spontaneous hypertension by sympathetic activation without increasing vasopressin secretion.

Mating type locus-dependent stability of the Kluyveromyces linear pGKL plasmids in Saccharomyces cerevisiae.

The linear killer plasmids, pGKL1 and pGKL2, from Kluyveromyces lactis stably replicated in mitochondrial DNA-deficient (rho 0) MATa or MAT alpha haploids of Saccharomyces cerevisiae, but were unstable and frequently lost in rho 0 MATa/MAT alpha diploids, suggesting that the replication of pGKL plasmids was under the control of the MAT locus. In MATa/MAT alpha cells of S. cerevisiae, the MAT alpha gene product (alpha 2) is combined with the MATa gene product (a1) and the resultant protein, a1-alpha 2, acts to repress the expression of haploid specific genes. Experiments showed that the K. lactis linear plasmids were stably maintained in rho 0 mata1/MAT alpha diploids, indicating that the a1-alpha 2 repressor interfered with the stability of pGKL2. It was revealed by computer analysis that the consensus sequence homologous to the a1-alpha 2 repressor binding site occurred within the coding regions of pGKL2 genes which were presumed to be essential for the plasmid replication. Since the plasmids were stably maintained in diploids of K. lactis, the mating type control must not be working there.

[Double minute chromosomes (DMs) in a case of acute myelomonocytic leukemia].

A 71-year old male was admitted to our hospital because of general malaise and fever. Peripheral blood showed Hb 8.1 g/dl, platelet 7.0 X 10(4)/microliters, and WBC 18.100/microliters with 64% leukemic cells. Bone marrow showed normocellularity with 73.4% leukemic cells. They were positive for peroxidase and alpha-naphthyl butyrate esterase stainings. Serum and urine lysozyme levels were elevated. He was diagnosed as having acute myelomonocytic leukemia (M 4 in FAB classification). Chromosome analysis of bone marrow cells showed 45, XY, -17, t (9; 17) (q22; p13) and double minute chromosomes (DMs) were observed in the 50 cells analyzed. A complete remission (CR) was obtained by DCMP regimen, but he relapsed as acute monocytic leukemia (M 5 b in FAB classification) and died 5 months after diagnosis. DMs appear to be rare in acute leukemia and the clinical and etiologic implications of DMs are discussed.