Contributing factors to intellectual impairment in patients with multiple lacunar infarctions]

The author investigated factors leading to intellectual impairment in patients with multiple lacunar infarctions. The subjects consisted of 40 patients with multi-infarct dementia (MID) and 17 nondemented patients with multiple infarctions (MI) who showed multiple lacunar infarctions in the deep penetrating arterial territory on CT. MID patients showed more marked and extensive periventricular lucency (PVL), a higher degree of ventricular index (VI) measured on CT, and were of a higher age, and had poorer activity of daily living (ADL) compared with MI patients. There were significant correlations between the PVL score, VI, ADL score, age and Hasegawa's dementia rating score (HDS). However, no significant differences in sex, site of infarct, and the count of low density areas reflected lacunar infarction on CT, and vascular risk factors were shown between MID and MI patients. Multiple regression analysis demonstrated that the PVL score and VI showed the highest partial correlations for HDS, and that the ADL score and age were also independently contributing factors. Our results suggest that deep white matter lesions observed as PVL on CT and ventricular enlargement were the most important factors contributing to intellectual impairment in patients with multiple lacunar infarcts, and that physical factors such as ADL and age can be considered to be related to the development of dementia.     

Distribution and characterization of immunoreactive corticotropin-releasing factor in human tissues

The distribution and characterization of immunoreactive corticotropin-releasing factor (I-CRF) in human tissues were examined using a rat CRF RIA, immunoaffinity chromatography, gel filtration chromatography, and high performance liquid chromatography. High concentrations of I-CRF were found in the hypothalamus and pituitary stalk. In addition, I-CRF was found in the posterior pituitary, thalamus, cerebral cortex, cerebellum, pons, medulla oblongata, spinal cord, and outside the brain and in the adrenal, lung, liver, stomach, duodenum, and pancreas. The major component of I-CRF from these tissues eluted in the position of rat CRF on gel filtration chromatography. High performance liquid chromatography of this major component showed two main peaks which eluted in the positions of CRF and oxidized CRF. These elution positions were the same in all tissues. These results indicate the presence of I-CRF outside the brain and suggest that this CRF is identical to hypothalamic CRF.     

Beneficial effects of severe sleep apnea therapy on nocturnal glucose control in persons with type 2 diabetes mellitus

Given the consequences of sleep apnea and coexisting diabetes, satisfactory treatment of both diseases is required. Our results of continuous glucose monitoring in severe sleep apnea diabetic patients before and during continuous positive airway pressure/CPAP therapy showed significant reduction of nocturnal glucose variability and improved overnight glucose control on CPAP.     

Effects of corticotropin-releasing hormone and dexamethasone on proopiomelanocortin messenger RNA level in human corticotroph adenoma cells in vitro

The effects of corticotropin-releasing hormone (CRH) and dexamethasone on proopiomelanocortin (POMC) mRNA levels in cultured pituitary adenoma cells were studied in 10 patients with Cushing's disease. As a control, POMC mRNA levels in cells from nonadenomatous tissues were examined in four patients. Human POMC mRNA in the cells was analyzed by Northern blot hybridization. Human POMC DNA probe hybridized with only a single size class of RNA (approximately 1,200 nucleotides) from the adenoma and nonadenoma cells of each patient. The size of POMC mRNA did not change through the culture or after incubation with CRH or dexamethasone. CRH increased POMC mRNA levels in these cells in a dose- and time-dependent manner. The minimum concentration of CRH required to elevate POMC mRNA levels in these cells exposed for 15 h was 0.1 nM. The minimum duration of 1 nM CRH treatment required to increase these levels was 3 h under our conditions. Inhibitory effects of 1 and 10 micrograms/dl dexamethasone on ACTH release and POMC mRNA levels in nonadenoma cells were greater than those in adenoma cells. These results suggest the following: (a) that the mRNA in cultured pituitary adenoma cells is qualitatively the same as that in vivo; (b) that responses of mRNA levels to CRH are time- and dose-dependent; and (c) that adenoma cells resist the inhibitory effect of dexamethasone on POMC mRNA levels and ACTH release.     

Immunoreactive corticotropin-releasing factor in human plasma.

Plasma immunoreactive corticotropin-releasing factor (I-CRF) levels were determined by using a human CRF radioimmunoassay and an immunoaffinity procedure. The basal plasma I-CRF level in normal subjects was 6 +/- 0.5 pg/ml (mean +/- SD). We found that most plasma I-CRF levels were affected by stress, negative feedback, and circadian rhythm. Basal I-CRF levels were high in patients with Addison's disease, Nelson's syndrome, hypopituitarism stemming from pituitary macroadenoma, and CRF- and adrenocorticotropic hormone-producing tumors. A very low, but significant, amount of I-CRF was detected (1-3 pg/ml) in patients with Cushing's syndrome, in corticosteroid-treated patients, and in a patient with hypothalamic hypopituitarism. These results suggest that a major component of plasma I-CRF is of hypothalamic origin, however, other extrahypothalamic tissues cannot be ruled out as a minor source of plasma I-CRF.     

Anatomical study of human adductor hallucis muscle with respect to its origin and insertion

The adductor hallucis muscle (ADH) is evolutionally and functionally important, but no detailed morphological data about this muscle in the human body is available. In the present study, we examined the origin and insertion of the oblique and transverse heads of the ADH. Forty-five feet (20 right, 25 left) of 34 cadavers (13 men, 21 women, average age of 80 years old) were used in the present study. The origin, insertion and nerve supplies of the oblique and transverse heads of the ADH were macroscopically examined in detail. Most commonly, the oblique head of the ADH arose from the bases of the 2nd, 3rd and 4th metatarsal bones, the plantar metatarsal ligaments spanned between the bases of the 2nd, 3rd and 4th metatarsal bones, the lateral cuneiform bone, the fibrous sheath of the tendon of the peroneus longus muscle and the long plantar ligament, and inserted into the lateral sesamoid bone of the great toe and the capsule of the 1st metatarsophalangeal joint. Most commonly, the transverse head of the ADH originated from the capsules of the 3rd and 4th (and occasionally 5th) metatarsophalangeal joint and the deep transverse metatarsal ligaments, and inserted into the lateral sesamoid bone of the great toe, the capsule of the 1st metatarsophalangeal joint and lateral surface of the base of the 1st proximal phalanx. This muscle was classified into four types based on the origin of its oblique head and was classified into three types based on the origin of its transverse head. The percent ratio of the weight of the oblique head to the total weight of all the intrinsic muscles of the foot was 9.4% ± 1.5, and the transverse head was 1.5% ± 0.6 (n = 14). The transverse head of ADH tends to be reduced in size in the human, but the oblique head is well developed with no sign of reduction.     

Anti-cancer drugs targeting fatty acid synthase (FAS)

Fatty acid synthase (FAS) is a key enzyme of the fatty acid biosynthetic pathway which catalyzes de novo lipid synthesis. FAS expression in normal adult tissues is generally very low or undetectable as majority of fatty acids obtained are from dietary sources, whereas it is significantly upregulated in cancer cells despite adequate nutritional lipid supply. Activation of FAS provides rapidly proliferating tumor cells sufficient amount of lipids for membrane biogenesis and confers growth and survival advantage possibly acting as a metabolic oncogene. Importantly, inhibition of FAS in cancer cells using the pharmacological FAS inhibitors results in tumor cell death by apoptosis whereas normal cells are resistant. Due to this differential expression of FAS, the inhibitors of this enzyme are selectively toxic to tumor cells and therefore FAS is considered an attractive therapeutic target for cancer. Several FAS inhibitors are already patented and commercially available; however, the potential toxicity of these FAS inhibitors remains to be tested in clinical trials. In this review, we discuss some of the potent FAS inhibitors along with their patent information, the mechanism of anti-cancer effects and the development of more specific and potent FAS inhibitors with lower side effects that are expected to emerge as anti-cancer treatment in the near future.