An automated rapid detection system using the quenching probe method for detecting interleukin 28B and inosine triphosphatase single nucleotide polymorphisms in chronic hepatitis C.

Single nucleotide polymorphisms (SNPs) in the interleukin 28B gene (IL28B) are good pretreatment predictors of anti-hepatitis C virus (HCV) therapy with interferon. SNPs of the inosine triphosphatase (ITPA) gene are associated with reduced haemoglobin levels during treatment with ribavirin. The i-densy™ (Arkray, Inc.), which is based on the quenching probe (QP) method, automatically detects target genes in blood samples by fluorescence quenching within 100 min. Using a QP and primer set, a gene amplification response is generated that can quickly and easily detect a specific gene's arrangement by fluorometry. The present study was conducted to compare the utility of i-densy (QP method) with that of conventional direct sequencing (DS) for detecting SNPs in the IL28B and ITPA genes in chronic hepatitis C patients. Between June 2011 and January 2012, 73 consecutive patients underwent genotyping of IL28B, and 54 patients underwent genotyping of ITPA. All of the patients were seropositive for HCV-RNA. The IL28B and ITPA genotypes were tested for bi-allelic polymorphisms in rs8099917 (T/T, T/G and G/G; minor allele, G) and rs1127354 (C/C, C/A and A/A; minor allele, A), respectively. The results obtained with the QP method were identical to those obtained with the conventional DS method. The frequency of the IL28B genotypes TT, GT and GG were 74%, 24.7% and 1.4%, respectively, and those of the ITPA genotypes CC, AC and AA were 68.5%, 29.6% and 1.9%, respectively. These results indicate that the i-densy using the QP method can automatically, quickly and easily identify genotypes of IL28B and ITPA.

Involvement of programmed cell death 4 in transforming growth factor-beta1-induced apoptosis in human hepatocellular carcinoma.

The programmed cell death 4 (PDCD4) gene was originally identified as a tumor-related gene in humans and acts as a tumor-suppressor in mouse epidermal carcinoma cells. However, its function and regulatory mechanisms of expression in human cancer remain to be elucidated. We therefore investigated the expression of PDCD4 in human hepatocellular carcinoma (HCC) and the role of PDCD4 in human HCC cells. Downregulation of PDCD4 protein was observed in all HCC tissues tested compared with corresponding noncancerous liver, as revealed by Western blotting or immunohistochemical staining. Human HCC cell line, Huh7, transfected with PDCD4 cDNA showed nuclear fragmentation and DNA laddering characteristic of apoptotic cells associated with mitochondrial changes and caspase activation. Transforming growth factor-beta1 (TGF-beta1) treatment of Huh7 cells resulted in increased PDCD4 expression and occurrence of apoptosis, also concomitant with mitochondrial events and caspase activation. Transfection of Smad7, a known antagonist to TGF-beta1 signaling, protected cells from TGF-beta1-mediated apoptosis and suppressed TGF-beta1-induced PDCD4 expression. Moreover, antisense PDCD4 transfectants were resistant to apoptosis induced by TGF-beta1. In conclusion, these data suggest that PDCD4 is a proapoptotic molecule involved in TGF-beta1-induced apoptosis in human HCC cells, and a possible tumor suppressor in hepatocarcinogenesis.

Involvement of the Ets-1 gene in overexpression of matrilysin in human hepatocellular carcinoma.

Although matrix metalloproteinases (MMPs) are thought to be involved in the invasion and metastasis of a variety of malignant tumors, including human hepatocellular carcinoma (HCC), the mechanisms for the expression of MMPs in HCC are not known. To understand the mechanism(s) of MMP expression, the expression of matrilysin (MMP-7) and several genes of the Ets transcription factor family was investigated in human HCC and hepatoma-derived cell lines. The role of Ets-1 gene expression in HCC was also studied. Analysis by semiquantitative reverse transcription-PCR revealed that MMP-7 and Ets-1 are overexpressed and closely associated in HCC. To clarify the role of Ets-1, hepatoma cells were transduced with human Ets-1 or targeted with the Ets-1-specific antisense oligonucleotides. Cells stably transduced with the Ets-1 gene showed increased MMP-7 expression compared to parental and mock-transfected cells. Cells targeted with Ets-1-specific antisense oligonucleotides showed reduced expression of MMP-7. Cotransfection of cells with a MMP-7 promoter-reporter gene plasmid and an Ets-1 expression vector yielded an increase in MMP-7 promoter activity in an Ets-1-responsive element-dependent manner. Taken together, these data suggested that the Ets-1 oncogene is up-regulated and involved in the overexpression of MMP-7 in human HCC and may contribute to the progression of HCC.

[Metastatic lung tumor from uterine leiomyosarcoma].

We herein present 2 cases of metastatic lung tumor derived from uterine leiomyosarcoma. In the case 1, a 59-year-old woman was admitted to our hospital to examine abnormal shadow detected on chest X-ray. She had undergone hysterectomy and oophorectomy for uterine leiomyosarcoma 19 months previously. A round 3 cm mass in the right lung (S10) was seen on chest X-ray and computed tomography (CT). No other distant metastases or local recurrence were found, and the right lower lobectomy was perfomed under the clinical diagnosis of metastatic lung tumor. Postoperative pathologic examination revealed the tumor as a metastatic leiomyosarcoma. The patient recovered uneventfully, and there have been no signs of recurrence for 26 months after the pulmonary resection. In the case 2, a 58-year-old woman, who had undergone hysterectomy and oophorectomy for uterine leiomyosarcoma 7 months previously, was admitted to our hospital for further examination of pulmonary tumors on chest X-ray. Two tumors were recognized in the left lung (S8 and S10) on chest X-ray and CT. No other distant metastases or local recurrence were found, and the left lower lobectomy was performed under the clinical diagnosis of metastatic lung tumors. Pathological examinations revealed smooth muscle cells with nuclear pleomorphism and high mitotic indices. The tumors proved to be lung metastases derived from uterine leiomyosarcoma. Postoperative course was uneventful. However, brain metastasis was found 1 month after the pulmonary resection, and she underwent resection of brain metastasis. Two months after the brain metastasectomy, local recurrence of the brain tumor developed and re-resection followed by stereotactic radiotherapy was performed. Furthermore, intrapelvic recurrence was found 4 months after the pulmonary resection. Exploratory laparotomy revealed the tumor was unresectable, and she received 4 courses of chemotherapy (paclitaxel and carboplatin). For metastatic lung tumor from uterine leiomyosarcoma, surgery has been considered the best choice. However, for patients with uterine leiomyosarcoma who cannot be treated surgically because of multiple metastatic tumors or poor surgical risk chemotherapy (paclitaxel and carboplatin) or stereotactic radiotherapy can be strategies.

Calphostin C-mediated translocation and integration of Bax into mitochondria induces cytochrome c release before mitochondrial dysfunction.

Calphostin C-mediated apoptosis in glioma cells was reported previously to be associated with down-regulation of Bcl-2 and Bcl-xL. In this study, we report that 100 nM calphostin C also induces translocation and integration of monomeric Bax into mitochondrial membrane, followed by cytochrome c release into cytosol and subsequent decrease of mitochondrial inner membrane potential (DeltaPsim) before activation of caspase-3. The integration of monomeric Bax was associated with acquirement of alkali-resistance. The translocated monomeric Bax was partly homodimerized after cytochrome c release and decrease of DeltaPsim. The translocation and homodimerization of Bax, cytochrome c release, and decrease of DeltaPsim were not blocked by 100 microM z-VAD.fmk, a pan-caspase inhibitor, but the homodimerization of Bax and decrease of DeltaPsim were inhibited by 10 microM oligomycin, a mitochondrial F0F1-ATPase inhibitor. Therefore, it would be assumed that mitochondrial release of cytochrome c results from translocation and integration of Bax and is independent of permeability transition of mitochondria and caspase activation, representing a critical step in calphostin C-induced cell death.

Ca2+/calmodulin-dependent protein phosphatase in bovine parotid gland: purification and characterization.

Calmodulin-dependent protein phosphatase (CaM-PPase) was isolated from bovine parotid gland by sequential application of DEAE-52, Affi-gel blue and calmodulin-affinity chromatography followed by gel filtration and high performance liquid chromatography. The enzyme was activated in the simultaneous presence of Ni2+ or Mn2+ and Ca2+ plus calmodulin. Ca2+/calmodulin-dependent activation of CaM-PPase was antagonized by inhibitors of calmodulin action, such as W-7 and trifluoperazine. Tryptophan fluorescence was quenched in the presence of Ni2+. CaM-PPase was a heterodimer. The molecular weights of large subunits which bound calmodulin (CaM) were 68 kD and 58 kD - the 68 kD subunit was predominant. Polyclonal antibodies against bovine calcineurin cross-reacted with both types of larger subunits. Using polyclonal antibodies against bovine calcineurin or the monoclonal antibody against subunit B of bovine calcineurin, the smaller molecular weight subunit (19 kD) was found to be immunologically identical to subunit B of bovine calcineurin. In bovine parotid gland, CaM-PPase was found both in acinar and duct cells.

Activation of protein kinases in canine basilar artery in vasospasm.

Subarachnoid hemorrhage (SAH) often leads to a long-term narrowing of cerebra! artery called vasospasm. To understand the molecular mechanisms in vasospasm, signal transduction of tyrosine kinase pathway and phosphorylation of myosin light chain (MLC) and calponin (CaP) in the basilar artery were studied. Vasospasm was produced in the canine basilar artery by a two-hemorrhage method, and vasocontraction was induced by a local application of KCI or serotonin to the basilar artery after a transclival exposure. Intracellular substrates of tyrosine kinase pathway, including Shc, Rafl, and extracellular-regulated kinases in the basilar artery, were activated after SAH, and the activation of Shc suggests stimulation of signal transductions from tyrosine kinase receptors, G-coupled receptors, or both. The activation of tyrosine kinase pathway in vasospasm also was supported by dose-dependent dilation of the spastic basilar artery on days 0 and 7 by topical application of genistein, a tyrosine kinase inhibitor, and associated marked inhibition of tyrosine phosphorylation of intracellular substrates, including Shc. In addition, the generation of protein kinase M, catalytic fragment of protein kinase C(alpha) (PKC alpha), in vasospasm on days 0 and 7 was inhibited in response to genistein, indicating an inactivation of mu-calpain. It is suggested, therefore, that the reversal of vasospasm by genistein is closely associated with the restoration of intracellular Ca2+ levels. However, the increased activities of Raf1 and extracellular-regulated kinases in vasospasm were declined on day 7 compared with those on day 0 or 2, suggesting that the activation of tyrosine kinase pathway is more closely associated with the early stage of vasospasm than with the late stage of vasospasm. The analysis by pyrophosphate polyacrylamide gel electrophoresis (PPi-PAGE) demonstrated three MLC bands in vasospasm on days 2 and 7, as well as in KCI- and serotonin-induced vasocontraction. Since PPi-PAGE resolves smooth muscle MLC into three bands in the MLC kinase (MLCK)-mediated phosphorylation and into a single band in the PKC-mediated phosphorylation based on the phosphorylation state, the current results suggest that MLC in vasospasm is phosphorylated by MLCK but not by PKC. In basilar artery, CaP was significantly down-regulated, and in addition, significantly phosphorylated on serine and threonine residues only in vasospasm on days 2 and 7. Although the significance of CaP phosphorylations in vivo still is controversial, CaP down-regulation and phosphorylation may attenuate the inhibition of Mg(2+)-ATPase activity by CaP and induce a potential enhancement of smooth muscle contractility in delayed vasospasm. Since CaP is phosphorylated in vivo by PKC, activated PKC in vasospasm may phosphorylate CaP. Thus, SAH stimulates tyrosine kinase pathway to increase intracellular Ca2+ and activate PKC, and the former activates MLCK to phosphorylate MLC, whereas the latter phosphorylates CaP but not MLC.

Proteasome inhibitors induce mitochondria-independent apoptosis in human glioma cells.

The proteasome inhibitors lactacystin and AcLLNal induced p53-independent apoptosis in two human glioma cell lines, and the apoptosis was accompanied by up-regulation of immunoreactive wild-type p53, p21Waf1, Mdm2, and p27Kip1. Pretreatment with cycloheximide decreased the induction of cell death independently of p53 protein status, suggesting that the up-regulation of short-lived proteins is associated with proteasome inhibitor-induced apoptosis. Caspase-3-like proteases were activated in the proteasome inhibitor-mediated apoptosis, and the induction of cell death was inhibited more effectively in the presence of z-VAD.fmk than in the presence of Ac-DEVD.fmk, suggesting that caspases other than caspase-3 are involved. Nonetheless, there were no significant alterations in levels of immunoreactive Bcl-2, Bcl-X(L), Bax, Bad, and Bak, nor any evidence of cytochrome c release into cytosol and dissipation of delta(psi)m. Thus, the proteasome inhibitor-induced apoptosis is mediated by a mitochondria-independent mechanism, and the once activated caspase-3 does not cause the cytochrome c release and the delta(psi)m disruption.

Correlation of somatosensory central conduction time with height.

To study the correlation between somatosensory central conduction time (CCT) and the subject's height, we recorded somatosensory evoked potentials (SEPs) from the neck and scalp elicited by median nerve stimulation in 72 normal young adults. We determined the CCT in each subject from peak-to-peak and onset-to-onset measurements. The mean value for the onset CCT was 6.2 +/- 0.4 msec and for the peak CCT, 5.7 +/- 0.5 msec. The peak CCT was significantly shorter but showed a wide range. There was a significant correlation between the onset CCT, but not the peak CCT, and height. Our findings confirm that the length of the central somatosensory pathway is proportional to the subject's height and indicate that the "conventional" peak CCT measurement of median nerve SEPs is inadequate.

Central conduction in somatosensory evoked potentials: comparison of ulnar and median data and evaluation of onset versus peak methods.

To compare central conduction in ulnar and median nerve somatosensory evoked potentials (SEPs), we recorded SEPs from the neck and scalp elicited by median and ulnar nerve stimulation in 46 normal young adults. We determined the central conduction time (CCT) in each subject from peak-to-peak and onset-to-onset measurements. The mean value of the onset CCT for the ulnar nerve SEP was 6.2 +/- 0.3 msec, and for the median nerve SEP, 5.9 +/- 0.3 msec. Onset CCT was significantly longer for the ulnar nerve SEP, and there was a significant correlation between onset CCT in both median and ulnar nerve SEPs and subject height. In contrast, the mean value of the "conventional" peak CCT for the ulnar nerve SEP was 5.6 +/- 0.6 msec, and for the median nerve SEP, 5.8 +/- 0.5 msec, with no significant difference between them. In addition, the peak CCT was not correlated with subject height in the ulnar or median nerve SEPs. Our findings suggest that onset CCT measurement is superior to the conventional peak CCT measurement for ulnar as well as median nerve SEPs, and confirm that the central conduction pathway for the ulnar nerve SEP is slightly longer than that for the median nerve SEP.

Peripheral and central conduction abnormalities in diabetes mellitus.

OBJECTIVES: To investigate peripheral and central somatosensory conduction in patients with diabetes. METHODS: The authors recorded sensory nerve action potentials and 5-channel somatosensory evoked potentials (SEPs) with noncephalic reference after median nerve stimulation in 55 patients with diabetes and 41 age- and height-matched normal subjects. The authors determined onset or peak latencies of the Erb's potential (N9) and the spinal N13-P13 and the cortical N20-P20 components, and obtained the central conduction time (CCT) by onset-to-onset and peak-to-peak measurements. RESULTS: Both onset and peak latencies of all SEP components were prolonged in patients with diabetes. The mean onset CCT in the diabetic group was 6.3 +/- 0.5 msec (mean +/- SD)-significantly longer than that in the control group (6.1 +/- 0.2 msec)-whereas no significant difference was found in the peak CCT. The amplitudes of N9 and N13-P13 components (but not N20-P20) were significantly smaller in the diabetic group. The peripheral sensory conduction velocity was also decreased in the diabetic group, but there was no significant correlation between peripheral conduction slowing and the onset of CCT prolongation. CONCLUSIONS: Diabetes affects conductive function in the central as well as peripheral somatosensory pathways. The CCT abnormality does not coincide with lowering of the peripheral sensory conduction. The current results do not favor a hypothesis that a central-peripheral distal axonopathy plays an important role in development of diabetic polyneuropathy.

Serum lipoprotein(a) levels before and after subtotal thyroidectomy in subjects with hyperthyroidism.

Lipoprotein(a) [Lp(a)], a lipoprotein that structurally resembles low-density lipoprotein (LDL), contains apolipoprotein(a) [apo(a)] and apolipoprotein B-100 (apo B). There exists a close inverse correlation between serum concentrations of LDL or apo B and concentrations of thyroid hormone in patients with thyroid disease, probably due to a change in LDL receptor activity. To clarify the relations between thyroid hormone and Lp(a), we measured serum Lp(a) levels in 13 hyperthyroid subjects before treatment (stage H), during the euthyroid stage induced immediately before performing a subtotal thyroidectomy (stage E), and during the hypothyroid stage observed transiently after the operation (stage L). The mean serum concentration of Lp(a) increased significantly (P = .01) from 9.4 mg/dL in stage H to 26.8 in stage L through the level of 15.5 mg/dL in stage E. There was no significant difference between the mean serum concentration of Lp(a) in these patients in stage E and healthy controls (14.2 mg/dL). There was a low but statistically significant negative correlation between the Lp(a) level and the serum free thyroxine (fT4) concentration (r = .31, P < .05). The results suggest that thyroid hormone is a potent modulator of Lp(a) metabolism.

Effects of aging on central conduction in somatosensory evoked potentials: evaluation of onset versus peak methods.

OBJECTIVES: To investigate effects of aging on peripheral and central somatosensory conduction, and evaluate onset-to-onset and peak-to-peak measurements of each component and central conduction time (CCT) in somatosensory evoked potentials (SEPs). METHODS: We recorded SEPs with non-cephalic reference from the Erb's point, the posterior (cv 6) and anterior neck, and scalp (Fz and P4) after left median nerve stimulation in 138 normal subjects aged between 20 and 78 years. We determined onset or peak latencies of the Erb's potential (N9), the spinal N13-P13 in cv 6-to-anterior neck montage and the N20-P20 in scalp leads. Onset CCT was defined as a transit time from N13-P13 onset to N20-P20 onset. In each subject, interpeak latencies of the 'N13' component in cv 6-to-Fz montage and the N20-P20 in P4-to-Fz montage were also defined as conventional peak CCT. RESULTS: Using multiregression analysis, we found that the onset or peak latencies of each SEP component were correlated with the subject's height and age. So were the onset CCTs: Onset CCT (in ms) = 2.549+2.041x(height in meters) + 0.005 x (age in years) (P<0.0001). The conventional peak CCTs as well as onset-to-peak durations of the N20-P20 were correlated with the subject's age but not height: Peak CCT(in ms) = 5.458+0.012x (age in years) (P<0.0005). CONCLUSION: Conductive function is affected by normal aging in the central as well as peripheral somatosensory pathways. The peak CCT is more affected by aging than the onset CCT. However, the onset-to-peak duration of the N20-P20 increased by 0.8 ms between the 4th and 7th decades, suggesting that the peak CCT increase in older people reflects the age-related changes in N20-P20 profile but not in the fastest central conduction. We therefore conclude that the onset CCT measurement is preferable to the peak CCT measurement when assessing the central somatosensory conduction.

Dipole orientation differs between high frequency oscillations and N20m current sources in human somatosensory evoked magnetic fields to median nerve stimulation.

The dipole orientation of equivalent current source for the high frequency oscillations (HFOs) above 300 Hz and that for the underlying N20m were compared. Somatic magnetic fields were recorded over the left hand somatosensory area to right median nerve stimulation at the wrist with a wide-bandpass (0.1-2000 Hz). The HFOs and underlying N20m were extracted by digital filtering of 300-900 Hz and 1-300 Hz, respectively. We found that the orientation of the HFOs and underlying N20m current sources differs and that the HFO source orientation shows a more divergent pattern than the N20m. These results suggest that the somatosensory HFOs are not generated from the pyramidal cell population in area 3b which produces the underlying N20m and that they may reflect activities of the non-pyramidal neuron population.

Gln27Glu beta2-adrenergic receptor variant is associated with hypertriglyceridemia and the development of fatty liver.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is associated with the metabolism of lipid, glucose and energy. Beta-adrenergic receptors play an important role in the regulation of energy expenditure, in part, by stimulating lipid mobilization through lipolysis. METHODS: To assess whether it is common for the beta2-adrenergic receptor (B2AR) gene polymorphisms in codons 16 and 27 to play a role in the development of fatty liver, we investigated 251 unrelated healthy Japanese males who were drug-free and showed no signs of heavy drinking. RESULTS: The allelic frequency of B2AR gene mutation in codons 16 and 27 did not differ between obese subjects (BMI>25.0 kg/m(2), n=151) and non-obese subjects (BMI

Association of the Pro90Ser CD36 mutation with elevated free fatty acid concentrations but not with insulin resistance syndrome in Japanese.

BACKGROUND: CD36 deficiency is reportedly an underlying factor about insulin resistance, defective fatty acid metabolism and hypertriglyceridemia in spontaneously hypertensive rat (SHR), and may be involved in the pathogenesis of insulin resistance and hyperlipidemia in humans. METHODS: We examined 831 adults undergoing health screening. The majority (780) was Pro90 homozygous for the CD36 gene product, but 51 displayed a CD36 mutation (2 homozygous and 49 heterozygous for Ser90). This is the major mutation site involved in CD36 deficiency in Japanese. RESULTS: Among parameters related to insulin resistance, there were no differences in body mass index (BMI), HDL cholesterol, total cholesterol, triglycerides, insulin and insulin resistance index (HOMA IR), or blood pressure between 91 normal subjects (45 male and 46 female) randomly selected from the 780 Pro90 homozygotes and the 51 (29 male and 22 females) CD36-deficient subjects (Ser90 homozygote and Pro90Ser heterozygote). Free fatty acid concentrations, however, were higher in Ser90 CD36 subjects than in Pro90 control subjects. CONCLUSIONS: The CD36Pro90Ser mutation is not necessarily related to the insulin resistance syndrome, but is associated with high free fatty acid concentrations in Japanese.

Ribose 1,5-bisphosphate inhibits fructose-1,6-bisphosphatase in rat kidney cortex.

Fructose-1,6-bisphosphatase is one of the regulatory enzymes of gluconeogenesis in kidney cortex. The effect of ribose 1,5-bisphosphate on fructose-1,6-bisphosphatase purified from rat kidney cortex was studied. Rat kidney cortex, fructose-1,6-bisphosphatase exhibited hyperbolic kinetics with regard to its substrate, but the activity was inhibited by ribose 1,5-bisphosphate at nanomolar concentrations. The inhibitory effect of ribose 1,5-bisphosphate on the fructose-1,6-bisphosphatase was enhanced in the presence of AMP, one of the inhibitors of fructose-1,6-bisphosphatase. Fructose-2,6-bisphosphate, which is an inhibitor of fructose-1,6-bisphosphatase, inhibited rat kidney cortex fructose-1,6-bisphosphatase activities at a low concentration of fructose-1,6-bisphosphate but a high concentration of fructose-1,6-bisphosphate relieved fructose-1,6-bisphosphatase from fructose-2,6-bisphosphate-dependent inhibition. On the contrary, fructose-1,6-bisphosphate was not effective for the recovery of fructose-1,6-bisphosphatase from ribose 1,5-bisphosphate-dependent inhibition. These results suggest that ribose 1,5-bisphosphate is a potent inhibitor and is involved in the regulation of fructose-1,6-bisphosphatase in rat kidney cortex.

Localized myxedema, associated with increased serum hyaluronic acid, and response to steroid pulse therapy.

A 66-year-old man presented with Graves' disease and widespread localized myxedema. Extensive lesions were present on the legs, feet, hands, and face. TSH receptor antibody (TBII) was markedly positive and the serum hyaluronic acid level was very high. Intravenous steroid pulse therapy was followed by oral therapy with gradual tapering. This regimen markedly improved the skin lesions and resulted in a decrease of the serum hyaluronic acid level. The findings suggest that steroid pulse therapy is effective for the treatment of extensive localized myxedema. In addition, the serum hyaluronic acid level may be a useful parameter for the follow-up of patients with this condition.

Pharmacological effects of dai-saiko-to on lipid biosynthesis in cultured human hepatocyte HepG2 cells.

The pharmacological effects of Dai-saiko-to, a Japanese and Chinese traditional medicinal mixture (Kampohozai), on lipid biosynthesis were investigated in cultured human hepatocyte HepG2 cells. The addition of Dai-saiko-to (0.5 mg/ml), which had no significant effect on cell proliferation, caused a marked decrease in the intracellular triglyceride content with no significant changes in the other lipid fraction. At the same time, the incorporation of 14C-acetate or 3H-glycerol into the triglyceride or diglyceride fractions also decreased significantly. These results suggest that Dai-saiko-to decreases hepatic triglyceride biosynthesis, which might contribute to a reduction in plasma VLDL levels.

Electrophysiological changes in diabetic neuropathy: from subclinical alterations to disabling abnormalities.

Clinical spectrum of diabetic neuropathy is variable; it may be asymptomatic, but once established as polyneuropathy, it is irreversible and may finally be disabling. To estimate the prevalence of subclinical diabetic polyneuropathy in the UAE, we undertook a pilot study by means of nerve conduction study (NCS) of peroneal motor and sural sensory studies in 60 diabetics with no symptoms of neuropathy. Neurological examination revealed clinical abnormalities suggesting polyneuropathy in 26 patients, 43% of the patients. NCS revealed abnormal values in 63% of the whole patients. Abnormal NCS was confirmed in 88% of the positive sign group. As to the negative sign group 44% had abnormalities in NCS. Prolonged F-wave latency was seen in 29% in no sign group and in 66% of the patients with positive signs. We found close association between neurological deficit score and abnormalities in NCS. Among various parameter of systemic nerve conduction study in subclinical patients, prolonged F-wave latency seems the commonest abnormality suggesting morphological changes in subclinical diabetic nerve. Decrease in amplitude of compound sensory action potential of sural nerve is another earlier abnormality, which is, then, accompanied by a fall in motor amplitude of peroneal nerve in advanced patients. Recently, our own group of Hirosaki has demonstrated that somatosensory central conduction time (CCT) between the spinal cord entry time and the arrival time to the sensory cortex is prolonged in diabetics. This abnormality might be partly responsible for the irreversible sensory deficits of diabetic neuropathy.