Plasma Ratios of Tryptophan and Tyrosine to Other Large Neutral Amino Acids in Manic-Depressive Patients

Abstract: The plasma ratio of each neutral amino acid (tryptophan (TRP), tyrosine (TYR), valine, isoleucine, leucine (LEU) or phenylalanine) to the sum of the other neutral amino acids was measured in 16 : manic and 14 : depressed patients. In the manics, there was a correlation between the psychomotor activity and the plasma TRP and LEU ratios. In the depressives, the depressed mood, retardation and global severity were correlated with the TRP ratio. The zotepine responders showed an increase in the TRP ratio after treatment. In the mianserin responders, the TYR ratio, which was high before the treatment, decreased to the normal range after the treatment. But, the plasma amino acid ratios remained unchanged in the patients treated with lithium carbonate or amitriptyhe. These results suggest that, in manic-depressive illness, there might be abnormalities in the metabolism of neutral amino acids, mainly of TRP and TYR, and that the plasma TRP and TYR ratios might be important indicators for determining the efflcacy of some drugs.     

Genetic alteration in carcinoid tumors of the lung.

Surgically resected specimens of 13 carcinoid tumors of the lung including nine typical carcinoids and four atypical carcinoids, and eight salivary gland type carcinomas (six mucoepidermoid carcinomas and two adenoid cystic carcinomas) were analyzed regarding p53 expression, loss of heterozygosity (LOH) in chromosome 3p, 9p, and K-ras mutation. The overexpression of p53 was identified in four atypical carcinoid tumors, one mucoepidermoid carcinoma, and one adenoid cystic carcinoma, however, none of typical carcinoids showed p53 immunoreactivity. LOH in 3p14 was demonstrated in three of seven informative cases in all tumors. LOH in 9p was demonstrated in two of five informative cases in all tumors. Two of three cases with LOH at 3p14 had a poor prognosis, one of which also had LOH at 9p. No mutation of the K-ras gene was observed in any of these tumors. These data thus indicate that p53 overexpression might distinguish atypical carcinoid tumors from typical tumors and might therefore be useful as an adjunct modality in the differential diagnosis of pulmonary carcinoid tumors. The presence of LOH at 3p14 or 9p may thus help to identify lung cancer patients with a poor prognosis.     

Cystic radiolucencies of carpal bones, distal radius and ulna as a marker for dialysis-associated amyloid osteoarthropathy.

Patients on long-term hemodialysis (HD) are known to develop amyloid osteoarthropathy, evidenced as cystic radiolucencies on X-rays of the affected joints. To study the relationship between cystic radiolucencies and amyloid osteoarthropathy in 394 patients, we classified the severity of the cystic radiolucencies seen in the wrist joint on a 4-point scale and evaluated the association between lesion severity (grade) and several parameters. Biopsy was performed in 8 patients with 11 bone cysts of the wrist joint who had been operated for carpal tunnel syndrome. HD for 10 years or longer, age 50 or older and the presence of carpal tunnel syndrome were associated with severe cyst rating. There was no association between lesion grade and serum level of PTH-C, aluminum or beta 2-microglobulin (B2M). Ten of the 11 biopsied bone cysts in 8 patients with carpal tunnel syndrome demonstrated amyloid deposits which reacted with B2M. We conclude that a cystic radiolucency observed in the wrist joint of a patient undergoing HD indicates the deposition of amyloid. The cyst grade provides a useful marker for the severity of amyloid osteoarthropathy in HD patients.     

Leiomyosarcoma originating in Meckel's diverticulum: Report of a case and a review of 59 cases in the English literature

A 49-year-old woman was referred to our hospital with complaints of epigastric colicky pain and high fever. Abdominal computed tomography and ultrasonography showed a solid tumor in the lower abdomen. Laparotomy revealed a neoplastic mass arising in Meckel's diverticulum; therefore, a segment of the ileum, including the tumor-possessing diverticulum, was resected with a lymph node dissection. A histologic examination confirmed the lesion to be leiomyosarcoma. In the English literature, 59 cases of leiomyosarcoma in Meckel's diverticulum were reported from 1941 to 1994. The majority of patients were in their 4th decade of life, with both sexes equally affected. The most frequent symptoms associated with this disease were abdominal pain with nausea, vomiting, and melena. The majority were larger than egg-size. Although Meckel's diverticulum is difficult to diagnose preoperatively, mesenteric arteriography may at times prove useful. The standard management of this particular tumor is wide segmental resection, including the tumor and diverticulum with lymph node dissection.     

Downhill esophageal varices due to superior vena cava syndrome

This study examined the incidence of downhill esophageal varices due to SVC syndrome. The presence of downhill esophageal varices was examined by esophagoscopy or autopsy. Downhill esophageal varices were detected in two of nine (22%) patients with SVC syndrome. One case was a 66-year-old male case who and underwent upper lobectomy for lung cancer in September 1985. He developed SVC syndrome due to recurrence in 1986 and died in 1987. Downhill esophageal varices wer in the upper esophagus by esophagoscopy and confirmed by autopsy. The another case was a 61-year-old female who developed carcinoma of the tongue in 1986 and lymph node metastasis to the mediastinum in 1987. Autopsy revealed downhill esophageal varices in the upper and middle esophagus. Eleven cases of downhill esophageal varices due to SVC syndrome reported in Japan were reviewed and discussed.     

Proton NMR studies on ischemic rat brain tissue.

The spin-lattice relaxation time (T1) of water protons and the cross-relaxation time (TIS) between irradiated protein protons and observed water protons were measured in order to study water-macromolecular interactions in ischemic rat brain tissues. Tissues were obtained by bilateral common carotid artery occlusion from stroke-prone spontaneously hypertensive rats. Water, Na, and K contents were measured in ischemic brain tissue at the same time. Water and Na content increased while the TIS value and K content decreased following ischemic insults. The T1 value did not change until 180 min after ischemia had been induced. Changes in the TIS value occurred earlier than changes observed for the T1 value, water, and electrolyte contents. Results indicate that the value of TIS may be useful for detecting cerebral ischemia and that the physical structure of water-macromolecular interaction may be altered soon after ischemic onset in brain tissue.     

Plasma carnitine concentrations in patients undergoing open heart surgery.

Carnitine is an essential cofactor for fatty acid (FA) metabolism, the predominant source of ATP in the normal aerobic heart. During myocardial ischemia, FA metabolism is impaired and tissue carnitine levels are depleted. Since the heart cannot synthesize carnitine, plasma carnitine could play an important role in maintaining myocardial carnitine levels during reperfusion. The purpose of this study was to determine the incidence of abnormal plasma carnitine concentrations in open heart surgery. Blood samples were obtained from eleven patients before, immediately after, and two hours after cardiopulmonary bypass (CPB). Total and free carnitine levels were significantly reduced immediately after CPB (p<0.01) and remained depressed until two hours after CPB (p<0.01 vs. pre CPB), while acyl carnitine levels were unchanged over the course of this study. These depressed free carnitine levels might affect cardiac metabolism in the heart after open heart surgery. Carnitine supplement might be a useful adjunct in the therapy after open heart surgery.     

A suspected case of alcoholic pellagra encephalopathy with marked response to niacin showing myoclonus and ataxia as chief complaints]

We report a 47-year-old alcoholic man with alcoholic pellagra encephalopathy (APE) showing myoclonus and ataxia as chief complaints. He had been a heavy drinker for 30 years. He had noticed appetite loss and subsequently showed a subacutely progressive gait disturbance. He had no history of diarrhea, dementia, or dermatitis. On admission, he showed severe alcoholic liver cirrhosis with a large amount of ascites, limbs and truncal ataxia, myoclonus of the limbs and areflexia, although his consciousness was alert and there were no sign of dermatitis. Though the plasma level of ammonia was normal, we started administration of amino acids suspecting hepatic encephalopathy. Symptoms showed no improvement, and subsequent administration of thiamine was also ineffective. A decreased serum level of niacin was demonstrated. After administration of nicotinamide, the symptoms improved gradually. This patient received a diagnosis of APE. Endemic pellagra, characterized by the classical triad of dermatitis, diarrhea and dementia, is known to be caused by a dietary deficiency of the niacin, and has now become very rare in developed countries. At present, pellagra is encountered most often in patients with chronic alcoholism, which is called APE. APE patients often show only disturbance of consciousness. Although several reports has described ataxia and myoclonus in patients with APE, APE patients with myoclonus and ataxia as chief complaints have not previously been reported. On autopsy cases, central chromatolysis of neurons in the dentate nucleus of the cerebellum, gracile and cuneate nuclei, and the Clarke's column has been demonstrated. The APE patients would show myoclonus and ataxia as their first symptoms. In conclusion, we would like to emphasize that administration of niacin should be started for the treatment of chronic alcoholic patients showing myoclonus and ataxia even without the classical triads found in endemic pellagra patients.     

TNF-alpha augments the expression of RhoA in the rat bronchus.

While nonspecific airway hyperresponsiveness (AHR) is a central feature of allergic bronchial asthma, the mechanism underlying the development of AHR is not clearly understood. We have previously demonstrated in vitro hyperresponsiveness of bronchial smooth muscle to acetylcholine (ACh) in rats that were actively sensitized and repeatedly challenged with aerosolized antigen. It has also been demonstrated that the ACh-induced, RhoA-mediated Ca(2+) sensitization is markedly augmented concomitantly with an increased expression and activation of RhoA protein in the bronchial smooth muscle of the antigen-treated rats. In the present study, we have investigated whether TNF-alpha, a proinflammatory cytokine which is involved in bronchial asthma, causes upregulation of RhoA mRNA and protein in the rat bronchus. Treatment of rat bronchial smooth muscle preparations with TNF-alpha (300 ng/ml for 24 hr) significantly shifted the concentration-response curve to ACh upwards, but did not alter the response to high K(+), when compared to that of control tissues. Levels of RhoA mRNA and protein in the TNF-alpha-treated bronchus were significantly greater than those in the control group. In conclusion, it is suggested that the augmentation of the ACh-induced contractile response evoked by TNF-alpha might be mediated by an upregulation of RhoA in rat bronchial smooth muscle.