A butter diet induces higher levels of n-3 PUFA and of n−3/n−6 PUFA ratio in rat serum and hearts than a safflower oil diet

The effects of a 47-week diet of butter or safflower oil as fat in combination with casein or soy protein as protein were observed for the serum concentrations of lipids and fatty acid compositions in rat serum and heart. Serum total cholesterol (Chol) did not differ among the four experimental diet groups. In the butter groups, significantly higher low-density lipoprotein (LDL)-Chol and lower high-density lipoprotein (HDL)-Chol were observed than in the safflower oil groups (p<0.005, respectively). Higher levels of α-tocopherol were found in the butter groups than in the safflower oil groups (p<0.05) and in the casein groups than in the soy protein groups (p<0.01). In comparison with the safflower oil groups, the butter groups showed higher n-3 polyunsaturated fatty acids (PUFA) contents and lower n-6 PUFA contents in serum and the hearts (p<0.005). The ratios of n-3/n-6 PUFA in the butter groups in serum, 0.26 and 0.18, and in the hearts, 0.37 and 0.36, (butter-casein diet and butter-soy protein diet, respectively) were higher than those of the safflower oil groups of under 0.01 in serum and 0.02 and 0.03 in the hearts (safflower oil-casein diet and safflower oil-soy protein diet, respectively) (p<0.005). In the soy protein groups, higher n-3 PUFA contents in the hearts were found than those of the casein groups (p<0.05). This study suggested that the butter diet induces higher levels of n-3 PUFA and a higher n-3/n-6 PUFA ratio than the safflower oil diet in rat serum and hearts over a long feeding period.     

Increased 8-hydroxyguanine in DNA and its repair activity in hamster and rat lung after intratracheal instillation of crocidolite asbestos.

Asbestos and man-made-mineral fibers are known to increase one type of oxidative DNA damage, 8-hydroxyguanine (8-OH-(Gua), in vitro. In this study, we analyzed the 8-OH-Gua level in DNA and its repair activity after a single intratracheal instillation of fibers (crocidolite or glass) or saline to Syrian hamsters or Wistar rats. The 8-OH-Gua level was measured with a high-performance liquid chromatography-electrochemical detector (HPLC-ECD) system. The 8-OH-Gua repair enzyme activity was determined with an endonuclease nicking assay using a 32P-labeled or fluorescently labeled 22mer DNA that contains 8-OH-Gua at a specific position. A significant increase in the 8-OH-Gua level in the lung DNA was observed 1 day after the exposure to crocidolite, as compared to the saline control. The repair activity was increased significantly at 7 days. On the other hand, after exposure to glass fibers, little or no increase of these carcinogenicity indicators was detected. These assays of 8-OH-Gua and its repair activity in short-term animal experiments will be useful for evaluating the carcinogenicity of fibers. This is the first report of the increase of 8-OH-Gua and its repair activity in the animal lung after the instillation of asbestos fibers.     

Clinical evaluation of intermittent hepatic arterial infusion therapy with CDDP and 5-FU for liver metastasis of colorectal cancer

Twenty-seven patients with liver metastasis from colorectal cancer were treated with intermittent intra-arterial infusion chemotherapy for 5 years starting from 1993. Five to ten mg of CDDP, 250 mg of 5-FU and/or 3-6 mg of Leucovorin were administered weekly. In the case of nonresponders, the dose of 5-FU was allowed to increase toward 500 mg. The above schedule was repeated as long as possible. The average number of administrations in 12 out of 27 unresectable patients was 28.7. The response rate was 50% (CR; 4 cases, PR; 2), with 2 NC and 3 PD. Four patients given 500 mg of 5-FU showed some response. The 50% survival period was 466 days, and the 1- and 3-year survival rates were 66.7% and 18.3%, respectively. The average number of administrations in the group of patients who underwent prophylactic treatment and resection of the metastasis was 33.1. During an average observational period 681 days, 7 patients (46.7%) had a recurrence in the liver. The 5-year survival rate was 85.7%. The patients who were treated with 250 mg 5-FU experienced no severe side effects, but one who was given 500 mg 5-FU developed a duodenal ulcer.     

Clinical analyses and short-term prognoses of neonates with subependymal cysts

Twenty-one neonates with subependymal cysts detected by neurosonography soon after birth were prospectively examined. The clinical and cranial sonographic findings were evaluated with respect to short-term prognosis. The prognosis was poor in 6 patients with congenital viral infection (4 with cytomegalovirus infection and 2 with rubella infection). Five patients also had neurodevelopmental abnormalities (2 with neonatal epileptic seizures, 2 with chromosomal abnormalities, and 1 with lissencephaly). The remaining 10 patients had normal psychomotor development. The incidence of congenital viral infection was statistically correlated with a poor neurodevelopmental outcome. A correlation did not exist between the short-term prognosis and each of the other clinical factors or cranial sonographic findings. Our evidence suggests that further investigation of possible subependymal cyst etiologies is required during a careful, long-term follow-up period.     

Integration of direction signals of image motion in the superior temporal sulcus of the macaque monkey

Using anesthetized and paralyzed monkeys, we have studied the visual response properties of neurons in the cortical area surrounding the middle temporal area (MT) in the superior temporal sulcus (STS). Systematic electrode penetrations revealed that there is a functionally distinct region where three classes of directionally selective cells with large receptive fields cluster. This region is anteriorly adjoined to the dorsal two-thirds of MT, has a width of 4-5 mm mediolaterally, and therefore may correspond to the dorsal part of the medial superior temporal area (MST), which was previously defined as a MT-recipient zone. One class of cells responded to a straight movement of patterns in the frontoparallel plane with directional selectivity (D cells: 217/422, 51.4%). The second class of cells selectively responded to an expanding or contracting size change of patterns (S cells: 66/422, 15.7%). These cells responded neither to a change in width of a slit of any orientation or any length, nor to a change in brightness. The third class of cells responded only to a rotation of patterns in one direction (R cells: 58/422, 13.7%). A majority of these cells (41/58) responded to the clockwise or counterclockwise rotation of patterns in the frontoparallel plane (Rf cells), while the rest responded to a rotation of patterns in depth (Rd cells). We will suggest that these cells acquire the ability to discover whole events of visual motion--i.e., unidirectional straight movement, size change (radial movement), and rotation--by integrating elemental motion information extracted by MT cells. The receptive fields of D, S, and Rf cells can be constructed by converging signals of MT cells, the preferred directions of which are arranged in parallel (D cells), radially (S cells), and circularly (Rf cells). The receptive fields of Rd cells can be constructed, in turn, by the convergence of signals of S cells.     

A patient presented with atypical paroxysmal kinesigenic choreoathetosis and Becker muscular dystrophy]

A 22-year-old man had choreatic movements in upper limbs, neck and trunk for over twelve years which were associated with dystonia in lower limbs upon initiating voluntary movements. The choreatic movement lasted for a few seconds and the dystonia lasted for a few minutes. He also had high serum CK levels and hypertrophic calf muscles. His muscle strength and deep tendon reflexes were normal. His choreatic movements fulfill the criteria for paroxysmal kinesigenic choreoathetosis (PKC). However, it was unclear what the symptom of dystonia was due to. From a muscle biopsy and DNA analysis, he was diagnosed as having Becker muscular dystrophy. Administration of anticonvulsant improved the dystonia as well as the choreatic movement, which showed that the dystonia was a symptom of PKC. Coincidence of choreatic movements and dystonias which had different lasting time in a patient of PKC was atypical and had not previously reported.     

Mitochondrial changes in motor neurons of homozygotes of leucine 126 TT deletion SOD1 transgenic mice

We investigated the time course of ultrastructural changes of mitochondria in the spinal cord of homozygotes of Leu126TTdel SOD1 (superoxide dismutase 1) with FLAG (signal sequence at the C‐terminal protein) transgenic mice (DF‐homo). Non‐Tg mice and wild‐type human SOD1 with FLAG epitope transgenic mice (WF) were investigated as controls for non‐onset Tg mice. Expansion and vacuolation of the mitochondrial matrix was exhibited in motor neurons in the anterior horns of DF‐homo Tg mice at the presymptomatic stage. Such mitochondrial degeneration became severe at the postsymptomatic stage. In contrast, expansion of the mitochondrial inner‐membrane space was not evident even at the terminal stage. Microvacuoles of cytoplasm and fibrillar inclusions were rarely shown from the early symptomatic stage. WF mice showed expansion and vacuolation of the mitochondrial inner membrane space at old age. Non‐Tgs showed no obvious change in mitochondria. Gold‐labeled human SOD1 immunoreactivity showed small amount of gold deposits in the vacuolated mitochondria. These results suggest that the expansion and vacuolation of mitochondrial matrix in the spinal cord of DF‐homo transgenic mice is the first pathological change, but that it is not directly caused by the aggregation of an abnormal human SOD1 protein in intermembrane space of mitochondria.     

Laboratory Evaluation of FR10024, a New Cephalosporin Derivative

FR10024 is a broad-spectrum antibiotic. The in vitro antibacterial activity of FR10024 against clinical isolates of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis is greater than that of any of the cephalosporins developed to date. Indole-positive Proteus, Enterobacter, and Citrobacter are resistant to FR10024, as is true for the other cephalosporins. However, more than half of the strains of Enterobacter and Citrobacter tested were susceptible to FR10024 at an inoculum of 10⁶ cells/ml. A single subcutaneous injection of FR10024 to mice with peritoneal infections due to S. aureus and several species of gram-negative bacilli gave a protective effect inferior to that of cefazolin but appeared to be superior to that of cephalothin. When given in two divided doses, however, the protective effect of FR10024 was enhanced and almost equaled that of cefazolin. The serum levels and rates of urinary recovery of FR10024 varied in different animal species. The mean peak serum level of FR10024 in humans after a single intramuscular injection of 500 mg was two times higher than that of cephalothin. The serum half-life after intramuscular injections of 250 and 500 mg was slightly shorter than that of cephalothin. After receiving 250 mg of FR10024 intramuscularly the urinary recovery rate was 87.7% in healthy volunteers. The biliary excretion rate of FR10024 was particularly high. The 24-h excretion of FR10024 in rats was 63.3%, this being six to seven times higher than that for cefazolin, which has the highest biliary excretion of the other known cephalosporins. When FR10024 was injected intramuscularly (20 mg/kg), it was found that the hepatic levels of FR10024 in rats were the highest of all the cephalosporins, including cefazolin, but the levels of FR10024 in other tissues were not as high as those of cefazolin.