Contribution of disulfide bonds to stability of the folding intermediate of α-lactalbumin

The secondary structure formed in disulfide reduced a-lactalbumin is investigated by CD spectrum and is compared with that of the folding intermediate of the disulfide intact protein. The peptide backbone structure of the reduced protein depends strongly on salt concentration in contrast to that of the intermediate. It is close to a random coil in the absence of salt, but it is almost the same as that of the intermediate at a high concentration of salt. The secondary structures of both the proteins undergo broad unfolding transitions when temperature is raised or when urea is added. The secondary structure of the reduced protein is less stable against both heat and urea. These results show that the disulfide bonds are not a determinant of the secondary structure formed at an early stage of folding, and they stabilize the secondary structure of the folding intermediate.     

Two cases of gastric cancer with peritoneal dissemination that responded to TS-1 without progression or recurrence for over 3 years

for over 3 years. A 67-year-old woman underwent distal gastrectomy for advanced gastric cancer. Histological examination of several nodules in the posterior gastric wall led to suspicion of peritoneal dissemination. Low-dose FP treatment was performed for only 5 days after surgery. Peritoneal dissemination was diagnosed at the time of surgery for postoperative abdominal hernia 20 months after the gastrectomy. TS-1 was administered postoperatively, and recurrence or progression has not been detected for 3 years 4 months. Another patient, a 68-year-old woman,underwent distal gastrectomy for advanced gastric cancer with multiple lymph node metastasis and peritoneal dissemination. TS-1 was administered after surgery, and no recurrence or progression has been detected for 3 years and 7 months. These cases suggest that TS-1 is a promising treatment for gastric cancer with peritoneal dissemination.     

A case of long survival of unresected gastric cancer with excellent QOL administered by S-1 alone

We report a case of unresectable gastric cancer, who had been treated with S-1 alone for 3 years without cancerous symptoms. The patient was a 66-year-old male. His diagnosis was advanced gastric cancer based on gastrofiberscopy. He underwent surgery on April 15, 2003. The tumor proved to be unresectable due to direct invasion of the pancreatic head, so only gastrojejunostomy was performed. On day 14 after surgery, the administration of S-1 alone was commenced at a dose of 100 mg per day in a 4-week course of medication at 2-week intervals. No side effects were noted. Moreover, his quality of life (QOL) was not disturbed, and he led an active social life throughout the course. Long survival was achieved by S-1 alone.     

Effects of Nicorandil on the cAMP-Dependent Cl− Current in Guinea-Pig Ventricular Cells

In guinea-pig cardiomyocytes, a cAMP-dependent Cl^? current (I_Cl,cAMP) flows through a cardiac isoform of the cystic fibrosis transmembrane conductance regulator (CFTR), which belongs to a family of the ATP-binding cassette (ABC) proteins. Although several K⁺-channel openers and sulfonylurea ATP-sensitive K⁺ (K_ATP)–channel blockers reportedly inhibit I_Cl,cAMP, effects of nicorandil on the Cl^? current have not been evaluated. This study was conducted to examine the effects of nicorandil on I_Cl,cAMP in isolated guinea-pig ventricular cells using patch clamp techniques. Nicorandil in concentrations higher than 300 μM enhanced the I_Cl,cAMP preactivated by 0.1 μM isoproterenol. The isoproterenol-induced I_Cl,cAMP was inhibited by 100 μM glibenclamide, but not by 100 μM pinacidil. SNAP (S-nitroso-N-acetyl-d,l-penicillamine, 10 μM), a nitric oxide (NO) donor, similarly enhanced the isoproterenol-induced I_Cl,cAMP. However, SG-86, a denitrated metabolite possessing K⁺ channel–opening action, failed to enhance the Cl^? current. When the I_Cl,cAMP was activated by 3-isobutyl-1-methylxanthine (IBMX, 30 μM), either nicorandil or SNAP failed to enhance the isoproterenol-induced I_Cl,cAMP. Thus, nicorandil enhances I_Cl,cAMP in guinea-pig cardiomyocytes through an increase in intracellular cGMP, although direct modulation of I_Cl,cAMP by NO cannot be completely excluded.     

Treatment of "the premonitory state of schizophrenia" with atypical antipsychotics]

"Premonitory symptoms and signs" before the full-blown stage of schizophrenia are recognized as abnormal expressions (signs) and symptoms of "early schizophrenia", as described by Nakayasu (1990). The following conclusions were derived from my examination of the effects of atypical antipsychotics on six patients suffering from 'the premonitory symptoms and signs' in 'the premonitory state of schizophrenia'. 1) Even though hyperventilation, fatigue and a depressive state existed in the foreground at the first medical examination, we suspected 'the premonitory state of schizophrenia', and investigated symptoms of 'early schizophrenia' as described by Nakayasu, in cases in which abnormal expressions such as stiff facial expression and specific tense and perplexed attitude were observed. 2) In cases in which 'the premonitory symptoms and signs' were observed, we introduced treatment with atypical antipsychotics as soon as possible. Hyperventilation and a depressive state, which were considered to be induced by 'the premonitory state of schizophrenia', disappeared as a result of the improvement of 'the premonitory symptoms and signs' by the atypical antipsychotics. 3) Risperidone, perospirone, and olanzapine were effective for so-called "positive early symptoms". Risperidone, which is expected to have an acute effect, was effective in cases in which early intervention was necessary. When a depressive state was secondarily induced by risperidone, a change to perospirone was useful. Furthermore, when risperidone and perospirone were not sufficiently effective, olanzapine improved 'the premonitory symptoms and signs'. 4) In cases in which so-called "negative early symptoms" and a decrease in the energy-potential, such as emotional blunting, were observed, olanzapine induced improvement. 5) In 'the premonitory state of schizophrenia', treatment with atypical antipsychotics should be maintained, for both the improvement of 'the premonitory symptoms and signs' and the prevention of progression to the full-blown stage. The dose and duration of the treatment with antipsychotics should be carefully modified, with consideration for the specificity of the life cycle and life events for each patient. In conclusion, treatment with atypical antipsychotics was useful for both the improvement of 'the premonitory symptoms and signs of schizophrenia' and the prevention of the development of pathogenesis.     

Characteristics of behavioral and psychological symptoms in the oldest patients with Alzheimer's disease

Background: Advancing age increases the risk of developing dementia. Recent studies have clarified characteristic cognitive changes in very old patients with dementia. Although non‐cognitive symptoms are frequent in dementia, relatively little attention has been paid to the nature of behavioral and psychological symptoms of dementia (BPSD). Methods: A retrospective review of a database was performed to compare 27 very old patients with Alzheimer's disease (AD) (onset age ≥ 85) with 162 less old patients (onset age < 85). Cognitive decline, ability to carry out activities of daily living (ADL), and overall severity were rated. BPSD were evaluated using a 16‐item questionnaire to the compare frequency of each symptom between old and very old groups. Results: Cognitive decline was equivocal in both old and very old groups. In contrast, very old patients were more impaired in ADL, and BPSD were more frequent in very old patients. Delusions, irritability, and delusional misidentification syndrome were frequent in both groups, but were more prominent in very old patients. Behavioral abnormalities such as excitement, delirium, reversed diurnal rhythm, and wandering were not prominent in old patients, but were frequent in very old patients. Conclusions: Very old AD patients presented more frequent BPSD than old AD patients. Troublesome behavioral abnormalities particularly prominent in the older patients might represent a heavy burden for caregivers.     

Deep Flexion-Oriented Bisurface-Type Knee Joint and Its Tibial Rotation That Attributes Its High Performance of Flexion

In 1989, we developed an artificial knee prosthesis that could accommodate the oriental lifestyle where people would sit more often on the floor than on a chair. The knee had a bisurface feature with an auxiliary joint of a ball and socket at the center of the posterior part aiming at an improved flexional function. The auxiliary joint functions not only to facilitate a rollback movement but also to add a rotational movement. It was investigated whether this knee prosthesis could show an internal rotation of the tibia during flexion such as the physiologic movement of the knee. The internal rotation of the tibia was evaluated for the patients who could sit on legs in the oriental style after total knee arthroplasty. The average flexion angle of patients who achieved this style of sitting was 144.1°, and the average internal rotation was estimated as 14.3° by a pattern matching method using a computer-assisted design system.