A case of cystadenocarcinoma of the liver

A case of cystadenocarcinoma of the liver is reported. The patient was a 73-year-old woman in whom a tumor was detected in the lateral segment of the liver during a health examination. Ultrasonograms and computed tomograms showed a multilocular cystic mass. Magnetic resonance imaging (MRI) showed a multilocular lowintensity mass, including a high-intensity portion and a portal branch compressed by the tumor. MRI with gadolinium showed an enhanced cyst wall. The cystic part of the tumor became smaller and the solid part became larger over a 1-month period, indicating that the tumor was malignant. Subsegmentectomy (S₃) was performed and cystadenocarcinoma with cystadenoma was diagnosed by histopathological examination. Identification of changes in the appearance of a tumor should be helpful for the differential diagnosis of cystadenoma and cystadenocarcinoma.     

Studies of the induction and maintenance of long-term graft acceptance by treatment with FK506 in heterotopic cardiac allotransplantation in rats

Immunosuppressive activities of the newly discovered FK506, isolated from Streptomyces tsukubaensis, were examined by using cardiac allotransplantation in the rat, and the mechanisms underlying induction and maintenance of FK506-induced long-term allograft survival were studied. Male rats of WKA (RT1k) and F344 (RT1lvl) strains were used as recipients and donors, respectively, and those of BN (RT1n) strain were used as third-party donors. Treatment with FK506, beginning from the day of allografting for 14, 10, or as few as 4 days, prolonged allograft survival significantly across the major histocompatibility barrier. The minimum doses for prolonging graft survival were 0.1 mg/kg/day by intramuscular treatment and 1.0 mg/kg/day by oral treatment. Treatment with FK506 at a dose of 0.32 mg/kg/day from day 4 until day 10 resulted in all the grafts surviving indefinitely and from days 5 to 10, half the grafts survived indefinitely, suggesting that the agent inhibited ongoing rejection. On the other hand, cyclosporine treatment at a dose of 20 mg/kg/day from day 2 did not prolong graft survival time statistically significantly. Induction of prolonged graft survival was not obtained by pretreatment of the prospective donor or recipient; prolonging effects were observed only when the agent was administered after allografting. Thus, the primary effect of the agent is exerted on responder lymphocytes reacting to the donor antigens in the induction phase of long-term graft acceptance. The mechanisms underlying the maintenance of long-term grafts were analyzed by testing the capacity of lymphocytes or serum of long-term graft-bearing rats to inhibit graft rejection in irradiated grafted hosts. Transfer of 2 x 10(8) lymphocytes from FK506-induced long-term F344 graft-bearing WKA rats resulted in indefinite survival of F344 heart allografts, but it did not prolong survival of third-party BN hearts. Transfer of 2.5 ml serum from long-term graft-bearing rats also prolonged graft survival of F344 hearts, but not BN hearts. These results suggest that donor strain-specific suppressor cells and humoral factor(s) are induced by treatment with FK506 in the presence of allografts, and that they play at least partial roles in the maintenance of long-term allograft acceptance.     

Molecular basis of severe myoclonic epilepsy in infancy

Severe myoclonic epilepsy (SMEI) or Dravet syndrome is caused by mutations of the SCN1A gene that encodes voltage-gated sodium channel alpha-1 subunit. Recently, we generated and characterized a knock-in (KI) mice with an SCN1A nonsense mutation that appeared in three independent SMEI patients. The SCN1A-KI mice well reproduced the SMEI disease phenotypes. Both homozygous and heterozygous knock-in mice developed epileptic seizures within the first postnatal month. In heterozygous knock-in mice, trains of evoked action potentials in inhibitory neurons exhibited pronounced spike amplitude decrement late in the burst but not in pyramidal neurons. We further showed that in wild-type mice the Nav1.1 protein is expressed dominantly in axons and moderately in somata of parbalbumin (PV) – positive inhibitory interneurons. Our immunohistochemical observations of the Nav1.1 are clearly distinct to the previous studies, and our findings has corrected the view of the Nav1.1 protein distribution. The data indicate that Nav1.1 plays critical roles in the spike output from PV interneurons and further, that the specifically altered function of these inhibitory circuits may contribute to epileptic seizures in the mice. These information should contribute to the understanding of molecular pathomechanism of SMEI and to develop its effective therapies.     

The efficacy and safety of laparoscopic nephrectomy in patients with three or more comorbidities

OBJECTIVES: Laparoscopic surgery for kidney treatment is a common procedure. However, the efficacy of this procedure in patients with several comorbidities has not been well investigated. We conducted a retrospective comparison of results of laparoscopic surgery between patients with several comorbidities and patients with no comorbidity to access the efficacy and safety of this procedure. METHODS: The subjects were 20 patients with three or more comorbidities (group A) and 46 patients with less than three comorbidities (group B). These 66 patients were 48 men and 18 women with a mean age of 62.3 years (age range, 24-83 years). The data from these two groups were compared for American Society of Anesthesiology (ASA) physical status score, previous surgical history, duration of surgery, estimated blood loss, tumor size, complications during and after surgery, conversion rates, time to oral intake, and length of hospital stay. RESULTS: The initial ASA score and age were significantly higher for the patients with comorbidities (P < 0.0001, P = 0.0008, respectively). All other variables before, during, and after surgery were similar for both laparoscopic groups. However, the incidence of atelectasis of laparoscopy was higher than that of open surgery. CONCLUSIONS: Laparoscopic nephrectomy for patients with comorbidities is safe and minimally invasive. Further investigation to prevent atelectasis is necessary.     

Angiotensinogen gene polymorphism as a risk factor for ischemic stroke.

While gene polymorphism for angiotensinogen (AGT) is reported to contribute to the regulation of blood pressure and salt sensitivity, its effect on the risk of ischemic stroke remains controversial. We hypothesized that polymorphism of the AGT gene could be a risk factor for ischemic stroke. Major clinical risk factors and the AGT gene M235T polymorphism were examined in 147 consecutive stroke patients and 133 healthy age-matched controls. All patients were categorized into four stroke types (single lacuna, multiple lacunae, large-artery atherosclerosis and branch atheromatous disease in brainstem) and two vascular groups (large and perforating arterial lesions). The AGT gene M allele significantly increased the risk of single lacuna, multiple lacunae and small arterial lesions, in male patients (p=0.029, 0.031 and 0.026, respectively). Synergistic effects of the AGT gene polymorphism and clinical risks were not observed. In conclusion, AGT M allele may present a risk of lacunar infarctions in Japanese men, independent of hypertension.     

Intraluminal thrombosis and growth-mechanism of giant intracranial aneurysms

12 giant intracranial aneurysms were studied by MRI. Intraluminal thrombosis was observed in 9 aneurysms. Thrombosis was found more frequently in larger aneurysms. Thrombi were formed posteriorly or inferiorly in the lumen of 4 among 5 IC-cavernous aneurysms. Location of the neck of the aneurysms and stagnation of blood flow influenced by gravity may be causative factors determining the location of thrombi. In 6 aneurysms intraluminal thrombi were inhomogeneous on MRI, suggesting that the thrombi had been formed at different times. New thrombi were formed between the aneurysmal wall and the old thrombus in 3 cases. Dissection of the aneurysmal wall by residual blood flow in the lumen or hemorrhage in the aneurysmal wall may be one of the growth mechanisms of giant intracranial aneurysms.     

Central inhibition of gastric motility by intravenously administered nicotine in rats

Effects of intravenously (i.v.) administered nicotine on gastric motility were investigated in urethane-anesthetized rats in which an intragastric balloon had been placed. I.v. administered nicotine at 75-300 nmole/kg dose-dependently decreased gastric motility. Decrease in gastric motility induced by nicotine at the dose of 300 nmole/kg was inhibited by intracisternally administered hexamethonium. Gastric motility was also decreased by intracisternally applied nicotine (1-10 nmole). These doses were much smaller than those by the intracerebroventricular route in our previous report. Bilateral vagotomy significantly suppressed basal gastric motility. In bilaterally vagotomized animals, nicotine at 1 mumole/kg but not 300 nmole/kg given i.v. significantly decreased the gastric motility maintained at a normal level by electrical stimulation of the vagus nerve. This nicotine-induced decrease in gastric motility, under conditions of electrical stimulation of the vagus nerve, was inhibited by pretreatment with phentolamine. These results suggest that a smaller dose of nicotine given i.v. activates nicotinic receptors in the brainstem and elicits vagally-mediated inhibition of gastric motility. Activation of peripheral alpha-adrenergic mechanisms together with that of central nicotinic mechanisms may be involved in the decreasing effects of a larger dose of nicotine on gastric motility.