[Structure and regulation of the expression of the proopiomelanocortin gene and processing of the precursor].
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Biomedical subjects
Publications and source records attributed to N Murakami.
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Described is a 57-year-old male with a complaint of a gait disturbance. On admission to hospital, he was suffering from almost complete paraplegia. Roentgenograms of the spine showed extensive destruction in the body of the second thoracic vertebra. Magnetic resonance computed tomography revealed a vertebral tumor that was compressing the vertebral cord. Thus, a laminectomy of the 1st to 3rd thoracic vertebra was performed to relieve the compression. Histological examination of the tumor showed it to be a metastatic vertebral tumor from a hepatocellular carcinoma (HCC). Subsequently, by abdominal computed tomography and an examination of the AFP serum level the existence of the HCC was confirmed. This is a very rare case of an HCC that was revealed by paraplegia caused by bone metastasis.
A molar ratio of free branched-chain amino acids to tyrosine (BTR) was determined in the plasma of patients with liver diseases using a new enzymatic method. In addition, clinical significance of BTR was studied by comparing particularly with that of Fischer's ratio (a molar ratio of branched-chain amino acids to aromatic amino acids (tyrosine+phenylalanine], which was obtained by conventional HPLC (Amino acid autoanalyzer, Hitachi 835). Following results were obtained: 1) Enzymatically determined branched-chain amino acids and tyrosine showed significant correlations with respective results obtained by HPLC (r = 0.937, 0.972). 2) Significant correlation was also found between enzymatically determined BTR and Fischer's ratio obtained by HPLC. Changes of BTR in clinical courses were found to be in parallel with those of Fischer's ratio. 3) BTR as well as Fischer's ratio correlated significantly with ICG R15, KICG, prothrombin time (%) and serum albumin level. 4) BTRs in patients with decompensated liver cirrhosis or with fulminant hepatitis were significantly lower than those in patients with acute or chronic hepatitis. In conclusion, new enzymatic assay of branched-chain amino acids and tyrosine as described here is quite simple method, and is also considered to be very useful parameter of the clinical conditions of patients with liver diseases, particularly representing the severity of liver diseases and the protein nutritional status.
Fifty-three patients with amyotrophic lateral sclerosis (ALS) were examined as to duration of illness, cause of death and need for respirator assistance. In 47 patients with ALS, respiratory failure is the most common cause of death accounting for 62% of all fatalities. Eleven patients with mechanical ventilation died of pneumonia and respiratory failure in four cases, atelectasis, gastrointestinal bleeding and asphyxia in one. Thirteen of 53 patients with ALS required mechanical ventilation. Six cases were put on a volume-limited respiratory or a pressure-limited respirator with O2 blender, and seven cases were put on a pressure-limited respirator only, which was unable to control oxygen concentration. As to the duration of their illness, patients with mechanical ventilation survived significantly longer than those without mechanical ventilation, so patients using a respirator could expect to live significantly longer than those without one. Patients using a volume limited respirator or a pressure-limited respirator with O2 blender had significantly longer duration of mechanical ventilation than those using a pressure-limited respirator only. It is concluded that a volume-limited respirator or a pressure-limited respirator with O2 blender is useful, if mechanical ventilation is needed, for ALS patients presenting with respiratory failure.
A sporadic case of spinocerebellar degeneration with prominent involvement of the motor system has recently been encountered. A 54-year-old man without family history noticed speech disturbance at the age of 46 and weakness in his right hand the following year. The muscle weakness and atrophy were slowly progressive and made walk impossible at the age of 50, when his dysphagia increased. At the age of 54, he was admitted to our hospital when neurological findings revealed marked amyotrophy of general skeletal muscle and tongue with fasciculation. Deep tendon reflexes were decreased. Cerebellar ataxia was impossible to evaluate because of profound muscle weakness. And sensory disturbance was suspected in the distal portion of the lower extremities. CT scan revealed progressive atrophy of the brain stem and cerebellum. The patient died at the age of 54 due to CO2 narcosis. The clinical course was 8 years. A summary of the pathological findings was as follows: 1) Marked neuronal loss of the anterior horn of the spinal cord and motor cranial nerve nuclei except for oculomotor nuclei, with mild degeneration of pyramidal tract below lumbosacral level. 2) Degeneration of cerebellipetal system, spinocerebellar tract, Clarke's column and the middle root zone and cerebellifugal system, dentate nucleus, superior cerebellar peduncles, and red nucleus. 3) Mild degeneration of pontine nuclei, inferior olivary nuclei, pontine transverse fibers, the middle and inferior cerebellar peduncles, cerebellar white matter and Purkinje cells as in OPCA.(ABSTRACT TRUNCATED AT 250 WORDS)
Study on detection of malignant cells in urinary sediments using supravital staining was described. We examined 96,554 specimens of urinary sediments for 2 years from January 1985 to December 1986. The results of microscopic urinalysis were compared with the cytological and histological diagnoses. Atypical cells were found in 138 patients, and 47 (34.1%) cancers were diagnosed histologically among them. These included 33 bladder cancer, 1 ureter cancer, 1 renal pelvic cancer, 2 prostate cancers, 1 rectal cancer, and 9 uterine cancers. Seven patients of them had not been under suspicion of malignancy yet before atypical cells were detected. Therefore microscopic urinalysis caused the triggers of cancer diagnoses. For bladder cancers, the positive rates in microscopic urinalysis were 43.4%, and those in urinary cytology were 52.4%. The positivity revealed higher in high-grade cancers than in low-grade. As compared with the results between microscopic urinalysis and urinary cytology in identical patients, the rate of correspondence between them was 89.5%. In 61.2% of positive and suspicious urinary cytology, atypical cells were not found. Atypical cells were seen in negative urinary cytology of 26 cases, and 5 cases of cancers were diagnosed histologically. These suggested that microscopic urinalysis as a screening for malignant cells was useful to detect urinary tract malignancy combining with urinary cytology.
A study was conducted to elucidate characteristics of circulatory parameters in patients with acute hepatic failure (AHF) employing Swan-Ganz catheter method and, in particular, ultrasonic quantitative flow measurement (QFM) system. The following results were obtained: 1) In five AHF patients who received Swan-Ganz catheter examinations, significant increases of cardiac index as well as decreased systemic vessel resistance were observed. 2) QFM in 11 patients with AHF revealed a significant increase of brachial artery blood flow (Br.F.), whereas common carotid blood flow (Ca.F.) was found to be significantly decreased. Thus, ratio of Ca.F./Br.F. showed a marked reduction as compared with that of control patients. 3) Vessel resistances measured by QFM were found to be significantly reduced in brachial artery, whereas markedly elevated in common carotid artery. 4) Those changes of circulatory parameters as described above were found to restore toward normal in parallel with the improvement of clinical features. 5) Vessel resistances of common carotid artery (Ca.R.) of AHF patients showed a significant negative correlation with CT values in the white matter of the brain, being regarded to well represent the degree of brain edema. In addition, in a case of AHF in whom intracranial pressure (ICP) was directly measured, time course of changes in Ca.F. was found to be in "mirror image" with that of ICP. Thus, it is strongly suggested that the increase of Ca.R. may well be induced, at least in part, by the elevated ICP in AHF patients.
A study was carried out using an experimental biliary infection model to investigate the pharmacokinetic characteristics and therapeutic effect of cefbuperazone in the rabbit. Thirty rabbits were divided into three equal groups; a control group of normal animals, a group of infected animals receiving no cefbuperazone, and a group of infected animals receiving 50 mg cefbuperazone/kg intramuscularly. The experimental infection was made by direct inoculation of a suspension of E. coli into the common bile duct after ligation. The results showed that extremely high levels of cefbuperazone were achieved in bile and tissues of the biliary tract and were higher than those in the blood. Moreover, the levels were maintained at effective concentrations even after 6 hours. Viable bacterial cells from bile and the gall-bladder were barely detectable 24 and 48 hours after infection in the cefbuperazone-treated group, whilst counts remained high in the other infected group. White blood cell counts were increased at 24 hours after infection but were significantly lower in the cefbuperazone-treated group. Histological examination revealed marked inflammatory changes in the gall-bladder and bile duct of infected, untreated animals but few, mild changes only were seen in cefbuperazone-treated animals. Similarly, total bilirubin and liver enzymes were markedly increased in infected animals, but transaminases and alkaline phosphatase were significantly lower in the treated compared to the untreated group. The findings indicate, therefore, that cefbuperazone can be a useful antibiotic in biliary infection.
Discussed is a case of a giant cell carcinoma that presented a high value of serum thyroglobulin. Histopathologically, this tumor had been diagnosed as being an anaplastic carcinoma that had transformed from a differentiated carcinoma, with calcification that was thought to have occurred from a preceding adenoma. To study the possibility of a malignant transformation, an immunohistochemical study of a specimen confirmed the production of thyroglobulin and vimentin, though the specimen stained negatively for keratin.
A 60-year-old man with a one-year history of agnogenic myeloid metaplasia was admitted to the hospital because of fever and a skin eruption. He had fever, anemia, hepatosplenomegaly, and a raised painful erythematous plaque in the face. The same kind of skin lesion developed thereafter at a venipuncture site in the left forearm. Bacterial cultures were negative. There was no response to antibiotic treatment. A biopsy specimen of the skin lesion revealed a dense dermal infiltration with mature neutrophils. A diagnosis of Sweet's syndrome was made. Fever and skin eruptions responded rapidly to prednisolone (PSL). Although the disease frequently recurred on rapid tapering of PSL, skin lesions cleared without scarring on a prolonged course of PSL. Four months after withdrawal of PSL, Sweet's syndrome recurred. A high dose PSL was given without benefit. He died of disseminated candidiasis.
Two cases of a leiomyosarcoma of the duodenum are reported. The first patient, a seventy-year-old woman, had experienced repeated instances of melena. She was diagnosed as having a leiomyosarcoma of the duodenum preoperatively, and was successfully given a pancreatoduodenectomy. The second patient, a fifty-one year-old woman, also had experienced instances of melena. Similarly, she was diagnosed an having leiomyosarcoma of the duodenum preoperatively, and was given a partial gastrectomy. A pathological examination showed little mitosis in either patient. The first patient is still alive three months after the operation, and the second patient also has been surviving for twelve years postoperatively.
We investigated the effect of microinjection of endogenous pyrogen or interleukin-1 (EP/IL-1) into 40 selected brain regions on the circulating leukocyte count in rabbits. The results show that injections into the rostral region of the hypothalamus, especially the preoptic and anterior hypothalamus, induce leukocytosis.
Valinomycin-induced potassium diffusion potential (delta psi, inside negative) in the liposomes made of phosphatidylcholine and various amounts of cholesterol was measured by uptake of 86Rb+, tetraphenylphosphonium (TPP+) or triphenylmethylphosphonium (TPMP+). In any liposome, the values of membrane potential obtained by 86Rb+ uptake (delta psi Rb) agreed well with those calculated from the imposed potassium concentration gradient using the Nernst equation, and were not affected by the presence of cholesterol. However, both delta psi TPP and delta psi TPMP showed smaller values than delta psi Rb when the cholesterol content in liposomes increased. delta psi TPMP at a stationary state was much smaller than delta psi TPP. The orientational order parameter of the lipids' bilayer with various cholesterol content was estimated from fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene. The results indicated that the permeation of TPP+ or TPMP+ into liposomes containing a large amount of cholesterol is strongly restricted by the high ordering of phosphatidylcholine acyl chains.
In order to investigate effects of thyroid hormone on ketone bodies metabolism, fasting levels of serum ketone bodies, serum free fatty acids (FFA), serum insulin (IRI), plasma glucagon (IRG) and plasma glucose were examined in 29 untreated patients with hyperthyroidism and 20 healthy subjects. In 21 patients the levels of serum ketone bodies were re-examined when euthyroidism was achieved after treatment. In all of healthy subjects and 17 patients changes in the levels of serum ketone bodies after oral glucose load were examined. The results were as follows: 1). Fasting levels of serum FFA and total ketone bodies (TK), acetoacetate (AcAc), 3-hydroxy-beta-butylate (3OHBA), ratio of 3OHBA to AcAc in the patients were significantly higher than those in healthy subjects. The levels of IRI, IRG or ratio of IRG to IRI in the patients were not different from those in healthy subjects. In the patients, the fasting level of TK was significantly correlated with the level of FFA. 2). After oral glucose load the levels of TK and FFA in the patients decreased gradually. 3). The fasting levels of TK and FFA in the patients decreased when euthyroidism was achieved after treatment. It was suggested that the fasting levels of serum ketone bodies in patients with hyperthyroidism elevated probably due to activated lipolysis.
Membrane vesicles from Halobacterium halobium create a large, inside negative membrane potential (delta psi) and small, inside alkaline pH gradient (delta pH) by illumination in 3 M NaCl. delta psi was the major component of a proton electrochemical potential (delta microH+) over a pH range from 5 to 8. After DCCD treatment of the vesicles, delta psi was replaced by delta pH due to the inhibition of the intrinsic delta pH----delta psi transformation process: delta psi formation in light is markedly retarded and an inversely large delta pH is established at these pHs. DCCD-caused changes in delta psi and delta pH were completely restored to the control level by the addition of monensin, an electroneutral Na+/H+ exchanger. The ratio of DCCD-caused change in delta pH and delta psi was identical to that of monensin-recovered delta psi and delta pH. The delta psi/delta pH ratio was approximately 0.8, that is, 100 mV of delta pH was transformed into 78 mV of delta psi. The present results indicate that the intrinsic activity of the DCCD-sensitive delta pH----delta psi transformation is mediated by an electroneutral Na+/H+ exchange.
While the heavy chain of rabbit skeletal muscle myosin is not phosphorylatable by casein kinase II, it turned out to be phosphorylatable after removal of all of the light chains. The phosphorylation site for the kinase was determined to be Ser-1 and/or Ser-2 at the amino terminus.
The effects of N,N'-dicyclohexylcarbodiimide (DCCD) and various ionophores on light-induced 22Na+-transport were studied in right-side-out membrane vesicles from Halobacterium halobium R1M1. The light-induced Na+ efflux was inhibited at the same DCCD concentration (greater than 40 nmol/mg protein) as required for inhibition of the Na+-dependent membrane potential (delta phi) formation. This supports our previous indication that the DCCD-sensitive, Na+-dependent transformation of pH-gradient (delta pH) into delta phi is mediated by Na+/H+-antiporter (Murakami, N. and Konishi, T. (1985) J. Biochem. 98, 897-907). FCCP or a combination of valinomycin and triphenyltin (TPT) inhibits the light-induced Na+ efflux in accordance with the notion of protonmotive force (delta mu H+)-driven antiporter. However, a marked lag in initiation of the Na+ efflux occurred in the presence of valinomycin, TPMP+, or a small amount of FCCP, suggesting that a gating step is involved in the Na+ efflux. On the other hand, the delta pH-dissipating ionophore TPT did not cause the lag. A simultaneous determination of delta phi, delta pH, and Na+ efflux rate at the initial stage of illumination revealed that the antiporter is gated by delta phi rather than delta mu H+.
On three epileptic conditions with common characteristics of almost continuous diffuse spike-and-wave discharges during sleep in EEG, clinical and electroencephalographic studies were undertaken to elucidate their pathophysiologies and interrelationships; namely on five cases of epilepsy with electrical status epilepticus during slow sleep (ESES), seven cases of a peculiar type of nonconvulsive status epilepticus in childhood (PNSE) and three cases of atypical benign partial epilepsy (ABPE). The dominant seizure types were absences and/or GTC in ESES, whereas they were focal motor seizures in PNSE and ABPE with more focalized epileptic discharges on EEGs than those in ESES. All the three conditions showed both features of generalized and partial epilepsies, although the former features were more prominent in ESES and the latter in PNSE and ABPE.