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Biomedical subjects

K Ohashi

Publications and source records attributed to K Ohashi.

At least 199 records · Page 11Linked to original sources
PubMed1999

Overexpressed lipoprotein lipase protects against atherosclerosis in apolipoprotein E knockout mice.

Lipoprotein lipase (LPL) is known to play a crucial role in lipoprotein metabolism by hydrolyzing triglycerides; however its role in atherogenesis has yet to be determined. We have previously shown that low density lipoprotein receptor knockout mice overexpressing LPL are resistant to diet-induced atherosclerosis due to the suppression of remnant lipoproteins. Plasma lipoproteins and atherosclerosis of apolipoprotein (apo) E knockout mice which overexpress the human LPL transgene (LPL/APOEKO) were compared with those of control apoE knockout mice (APOEKO). On a normal chow diet, LPL/APOEKO mice showed marked suppression of the plasma triglyceride levels compared with APOEKO mice (54 vs. 182 mg/dl), but no significant changes in plasma cholesterol and apoB levels. Non-high density lipoproteins (HDL) from LPL/APOEKO mice had lower triglyceride content, a smaller size, and a more positive charge compared with those from APOEKO mice. Cholesterol, apoA-I, and apoA-IV were increased in HDL. Although both groups developed hypercholesterolemia to a comparable degree in response to an atherogenic diet, the LPL/APOEKO mice developed 2-fold smaller fatty streak lesions in the aortic sinus compared to the APOEKO mice. In conclusion, overproduction of LPL is protective against atherosclerosis even in the absence of apoE.

Animals↗
PubMed1999

[Fractures easily missed by conventional radiographic diagnosis].

Although conventional radiography is the mainstay for diagnosing fractures, there are multiple conditions in which a fracture can be overlooked by the radiologist. This report focuses on the radiographic findings of various presentations of fractures including (1) minimally displaced fractures, (2) avulsion fractures, (3) stress fractures, (4) incomplete fractures and physeal injuries in children, and (5) occult fractures complicated with overt injury. Radiologists need to be familiar with these relatively common entities and aware of the limitations of radiography for fracture diagnosis; there are cases that can be diagnosed clinically without radiographic findings of cortical disruption. Repeated radiographic examination, CT, or MRI may be indicated depending on the clinical situation. The involvement of radiologists in the routine interpretation of conventional radiographs in trauma settings is encouraged to improve the detection of subtle fractures.

Bone and Bones↗
PubMed1999

A case of 43-year-old fighter pilot with bronchial asthma.

A Japan Air Self-Defense Force (JASDF) fighter pilot with adult onset atopic bronchial asthma was successfully returned to flying status. This was against the common wisdom of most Japanese military flight surgeons. Bronchial asthma generally results in permanent disqualification from flying duties because of possible acute incapacitation during flight. This JASDF pilot was treated with inhaled medications, including beclomethasone, for 6 mo with suppression of all clinical symptoms. All medications were discontinued and the pilot was observed for another 7 mo before resumption of flying status. This aeromedical disposition was based on the thinking that his long asymptomatic period indicated bronchial inflammation was resolved, bronchial reactivity was improved, and thus the risk of exacerbation was reduced.

Adult↗
PubMed1999

[Memoirs on Chlorodyne and Shinyaku].

Dr. J. Collins Browne, a British army surgeon in India, invented a secret remedy for cholera-infected patients in the fifth decade of the 19th century. After his resignation from the army, the formula was given to a pharmacist in London for the purpose of manufacture and marketing as a patented medicine named Chlorodyne. Chlorodyne was well-accepted as paregoric for several decades. The formula of Chlorodyne was adopted in the 3rd Revision of the British Pharmacopoeia (1885) as "Compound Tincture of Chloroform and Morphine." In 1906, the 3rd Revision of Japanese Pharmacopoeia listed "Compound Tincture and Morphine" according to the formula of the 4th Revision of British Pharmacopoeia (1898). References written in 1870 and 1873 recorded the importation of Chlorodyne to Japan. In 1871, Dr. Jyun Matsumoto, Chief Military Surgeon Major General advised the manufacturers of traditional medicines to produce patented medicines to spread in western countries. Preparations of formula seeming to resemble Chlorodyne was named "Shinyaku" and were marketed from 1872. The name Shinyaku represented a medicine of marvellous efficacy, because the word split, Shin and Yaku, means "divine or almighty" and "medicine," respectively. Although the orginal formula of Shinyaku was not preserved, modifications of the formula were made to meet legal restrictions over the change of time. Needless to say, Morphine hydrochloride, Diluted hydrocyanic acid and tincture of Indian hemp were replaced with other ingredients to assure safety and lately Chloroform deleted from the formula as well. Shinyaku enjoyed good sales for a long time owing to its efficacy of restorative and refrigerant.

Chloroform↗
PubMed1998

Effect of genetic differences in omeprazole metabolism on cure rates for Helicobacter pylori infection and peptic ulcer.

BACKGROUND: Omeprazole is metabolized by S-mephenytoin 4'-hydroxylase (CYP2C19) in the liver. In persons with a poor-metabolizer genotype for CYP2C19, the therapeutic efficacy of omeprazole may be increased. OBJECTIVE: To investigate whether CYP2C19 genotype status is associated with cure rates for Helicobacterpylori infection and peptic ulcer achieved by using dual therapy with omeprazole and amoxicillin. DESIGN: Prospective cohort study. SETTING: University hospital and health service center in Hamamatsu, Japan. PATIENTS: 62 patients with peptic ulcer and H. pylori infection. INTERVENTION: Omeprazole and amoxicillin. MEASUREMENTS: CYP2C19 genotype status and cure rates for H. pylori infection and peptic ulcer. RESULTS: Cure rates for H. pylori infection were 28.6% (95% CI, 13.1% to 48.7%), 60% (CI, 38.6% to 83.0%), and 100% (CI, 66.4% to 100%) in the rapid-, intermediate-, and poor-metabolizer groups, respectively. Healing rates for both duodenal and gastric ulcer in the three groups were roughly parallel with cure rates for H. pylori infection. CONCLUSION: The results of the genotyping test for CYP2C19 seem to predict cure of H. pylori infection and peptic ulcer in patients who receive dual therapy with omeprazole and amoxicillin.

Adult↗
PubMed1998

Propranolol attenuates haloperidol-induced Fos expression in discrete regions of rat brain: possible brain regions responsible for akathisia.

Neuroleptics induce several extra-pyramidal side effects, such as akathisia, acute dystonia and parkinsonism. Although recently developed atypical neuroleptics ameliorate some of these side effects, akathisia remains a common and severely distressing adverse reaction. Several drugs are reported to be of clinical use for the pharmacological treatment of akathisia. In particular, the beta-adrenoceptor blocker, propranolol, has been widely used for the treatment of akathisia, but it does not ameliorate other extra-pyramidal side effects. To identify the neural substrates of akathisia, we investigated the effects of propranolol on haloperidol-induced Fos expression in rat brain. Haloperidol (1 mg/kg) induced Fos-positive nuclei in several regions of the brain, including the cingulate cortex area 3, piriform cortex nucleus accumbens, caudate-putamen, ventral lateral septum and parietal cortex. Pretreatment with propranolol (5 mg/kg) reduced the number of Fos-positive nuclei in the cingulate cortex area 3, the piriform cortex and area 1 of the parietal cortex. Injection of vehicle by itself tended to increase Fos expression in the cingulate cortex area 3 and the piriform cortex. Considering the functions of these brain regions, we speculate that the most plausible neural framework for haloperidol-induced akathisia involves area I of the parietal cortex, but possible roles for the cingulate cortex area 3 and the piriform cortex cannot be ruled out.

Adrenergic beta-Antagonists↗
PubMed1998

Cholesterol lowering in low density lipoprotein receptor knockout mice overexpressing apolipoprotein E.

Apo E is a key molecule in the lipoprotein metabolism; thus, genetic manipulation of apo E may prove useful in the treatment of hypercholesterolemia. To test the feasibility of this idea, we have generated low density lipoprotein receptor (LDLR) knockout mice that overexpress the rat apo E transgene (ETg+/+:LDLRKO), and compared their plasma lipoprotein profiles with those of nonexpressing LDLR knockout mice (ETg-/-:LDLRKO). On a normal chow diet, the mean plasma cholesterol level of ETg+/+:LDLRKO mice was significantly lower than that of ETg-/-:LDLRKO mice (189 versus 240 mg/dl, P < 0. 01). The LDL fraction was selectively reduced in the ETg+/+:LDLRKO mice. Despite the challenge with an atherogenic diet, cholesterol lowering was persistently observed and fatty streak lesions in the aortic sinus were significantly suppressed in the mice overexpressing apo E. These results imply that stimulation of hepatic production of apo E may be used as a promising adjunctive therapy for homozygous familial hypercholesterolemia.

Animals↗
PubMed1998

Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization.

Rac is a small GTPase of the Rho family that mediates stimulus-induced actin cytoskeletal reorganization to generate lamellipodia. Little is known about the signalling pathways that link Rac activation to changes in actin filament dynamics. Cofilin is known to be a potent regulator of actin filament dynamics, and its ability to bind and depolymerize actin is abolished by phosphorylation of serine residue at 3; however, the kinases responsible for this phosphorylation have not been identified. Here we show that LIM-kinase 1 (LIMK-1), a serine/threonine kinase containing LIM and PDZ domains, phosphorylates cofilin at Ser 3, both in vitro and in vivo. When expressed in cultured cells, LIMK-1 induces actin reorganization and reverses cofilin-induced actin depolymerization. Expression of an inactive form of LIMK-1 suppresses lamellipodium formation induced by Rac or insulin. Furthermore, insulin and an active form of Rac increase the activity of LIMK-1. Taken together, our results indicate that LIMK-1 participates in Rac-mediated actin cytoskeletal reorganization, probably by phosphorylating cofilin.

Actin Depolymerizing Factors↗
PubMed1998

Identification of testis-specific (Limk2t) and brain-specific (Limk2c) isoforms of mouse LIM-kinase 2 gene transcripts.

LIM-kinase 1 (LIMK1) and LIM-kinase 2 (LIMK2) are members of a novel serine/threonine kinase subfamily with structural features composed of N-terminal two LIM domains, an internal PDZ-like domain, and a C-terminal protein kinase domain. We recently identified and characterized the mouse Limk2 gene and two Limk2 transcripts (Limk2a and Limk2b) coding for proteins with distinct N-terminal LIM structures. Here we describe two additional transcripts of the mouse Limk2 gene. One is a 1.7-kb transcript, termed Limk2t, which is specifically expressed in the testis and codes for an N-terminally truncated form of LIMK2 consisting of only a part of a PDZ-like domain and a protein kinase domain. The other is a transcript, termed Limk2c, which is specifically expressed in the brain and codes for a protein with a 6-amino-acid insert within the protein kinase domain. Exons specific to the 5'-terminal extra sequence of Limk2t and the insert sequence of Limk2c locate between exons 5-6 and exons 8-9 in the mouse Limk2 gene, respectively. Testis- and brain-specific expression of Limk2t and Limk2c suggests specific roles in these tissues.

Alternative Splicing↗
PubMed1998

Preferential expression of the gene for a putative inositol 1,4,5-trisphosphate receptor homologue in the mushroom bodies of the brain of the worker honeybee Apis mellifera L.

A gene expressed preferentially in the mushroom bodies of the brain of the worker honeybee Apis mellifera L. was identified by the differential display method and its cDNA was isolated. The cDNA fragment of 534 bp (clone A1) contained an open reading frame encoding 177 amino acid residues having 78, 72, 70, 59 and 55% sequence identities with the inositol 1,4,5-trisphosphate (IP3) receptors of Drosophila melanogaster, Xenopus laevis and humans (types 1, 2 and 3), respectively, suggesting that it encodes a putative IP3 receptor homologue of the honeybee. In situ hybridization revealed that the gene encoding clone A1 was expressed preferentially in the mushroom bodies and not in the optic lobes, antennal lobes and central bodies; in the mushroom body, it was expressed strongly in the large type Kenyon cells and weakly in the small type Kenyon cells. Reverse transcription polymerase chain reaction analysis showed that the gene was expressed strongly in the head and weakly in the antennae, legs, thorax, and abdomen. These results suggest that the A1 gene product plays a crucial role in neural transmission in the mushroom bodies of the worker bee brain.

Amino Acid Sequence↗
PubMed1998

Hyperthermo-chemo-hypoxic isolated liver perfusion for hepatic metastases: a possible adjuvant approach.

As a possible intraoperative adjuvant approach to treating hepatic metastases we developed a method of hyperthermo-chemo-hypoxic isolated liver perfusion in combination with hepatic resection. This method was applied to 11 patients with colorectal hepatic metastases between 1992 and 1995. One patient died on postoperative day 14 of hepatic failure (9% mortality), the cause of which was live temperature that reached 42.9 degree C, which seems to be the maximum limit for thermal toxic effect on the human liver. The other 10 patients tolerated the perfusion well, with mild hepatic and non systemic toxicity after minor or even major hepatic resection; the serum aminotransferase and total bilirubin levels returned to normal levels by postoperative day 14. Only one of eight patients (13%) for whom cytotoxic drugs were added to the perfusate (mitomycin C 10 micrograms/ml or cisplatin 2 micrograms/ml) had hepatic recurrence by 19 months after the perfusion (mean follow-up 25.8 months; median 23 months; range 8-57 months). Two patients were alive with no evidence of disease at 13 and 57 months, respectively after the perfusion; the other five patients had postperfusion extrahepatic recurrences (median: 19 months; range 7-20 months). In contrast, hepatic metastases recurred 7 and 20 months after the perfusion, respectively, in the two patients not given a cytotoxic drug.

Aged↗
PubMed1998

Pancreatic metastasis from a lung cancer. Preoperative diagnosis and management.

A case of a surgically resectable solitary metastasis to the pancreas from a lung cancer, confirmed by immunohistochemical staining (PE-10), is reported. ERCP revealed meniscoid interruption of the main pancreatic duct, which is uncommon in patients with primary pancreatic cancers of the pancreas in our hospital. This patient lived for 29 mo after the surgical resection of the pancreatic lesion. Therefore when metastasis limited to the pancreas is evident on clinical imaging, surgical management may be more optimal than other treatment approaches.

Adenocarcinoma↗
PubMed1998

Sleep apnoea in well-controlled myasthenia gravis and the effect of thymectomy.

We conducted overnight polysomnographic sleep studies of 16 patients (5 men and 11 women) with clinically well-controlled myasthenia gravis (MG). The subtypes of MG were IIA (3 patients), IIB (11 patients), IV (1 patient) and V (1 patient). Twelve patients were found on polysomnography to have obstructive and/or central types of the sleep apnoeas (SA). Their mean age was 42.4, SD 16.4 years, and the mean duration of MG was 7.4, SD 6.96 years. SA was not detected in 4 patients whose mean age was 30.8, SD 10.71 years and who had manifested MG for a mean duration of only 0.9, SD 0.65 years. Thus, patients with a longer duration of MG tended to have more SA. In 9 of the 12 SA patients, polysomnographic studies were repeated following thymectomy. SA had resolved in 6 patients, but persisted in 3. These findings suggest that SA is a possible clinical manifestiation of MG and that nocturnal dysfunction of both peripheral and central colinergic systems may be involved.

Adult↗
PubMed1998

Long-term prognosis of non-shunt operation for idiopathic portal hypertension.

This report presents 46 Japanese patients with idiopathic portal hypertension (IPH) in whom non-shunt operation was performed for the management of esophageal varices. Non-shunt operation included transthoracic esophageal transection (Sugiura's procedure) in 37 patients, transabdominal esophageal transection (TAET) in 3 patients, and Hassab's procedure in 6 patients. Rates of postoperative variceal eradication were: 78.4% by Sugiura's procedure; 100% by TAET; and 50% by Hassab's procedure. The cumulative rates for recurrent varices and recurrent bleeding were 3.9%, and 5.1%, respectively, at 5 years, and 8.9% and 9.8% at both 10 and 15 years. Only 3 patients required additional endoscopic injection sclerotherapy to treat recurrent varices. Although 3 patients developed upper gastrointestinal bleeding, the source of hemorrhage was esophageal varices in 1, and portal hypertensive gastropathy in 2; none of the patients died from bleeding. Actuarial survival for all patients was 87.5% at 5 years, 77.9% at 10 years, and 58.8% at 15 years. There were no deaths within the first 30 days after surgery. These results show that non-shunt operation is useful in preventing bleeding from esophageal varices in patients with IPH.

Adolescent↗
PubMed1998

Attenuation by ACE inhibitor drugs of alpha-adrenoceptor sensitivity in human vessels: possible differences related to drug lipophilicity.

AIMS: We investigated the effect of angiotensin converting enzyme inhibitors (ACEIs) on postsynaptic adrenoceptor sensitivity and compared the effect of the lipophilic ACEI, quinapril, and that of hydrophilic agent, enalapril in human vessels. METHODS: Alpha-adrenoceptor sensitivity was evaluated using the dorsal hand vein compliance technique. The dose-response curves of vasoconstriction to phenylephrine and prostaglandin F2alpha were obtained in healthy male volunteers. RESULTS: The ACEIs shifted the dose-response curve of phenylephrine to the right and raised the median effective dose (ED50; 189.3 (57.6 ng min(-1)) of phenylephrine. Following quinapril administration, ED50 increased to 481.1 (101.8 ngmin(-1) compared with 266.8 (55.8 ngmin(-1) after enalapril (95% CI for differences; 31.1-397.5 ng min(-1)). Quinapril administration had no effect on the dose-response curve of PGF2alpha. CONCLUSIONS: ACE inhibition attenuates alpha-adrenoceptor sensitivity in human vessels. The effect of quinapril, a lipophilic ACEI, was greater than that of enalapril, a hydrophilic ACEI. Lipophilic ACEIs may be more potent in vasodilating effect than hydrophilic ACEIs. Angiotensin II concentration in tissue rather than that in plasma may contribute to the alpha-adrenoceptor sensitivity of the vessels.

Adrenergic alpha-Antagonists↗