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Lipoprotein glomerulopathy (LPG) is a hereditary disorder characterized by intraglomerular lipoprotein thrombi and increased serum apolipoprotein (apo) E. Patients with LPG usually manifest with nephrotic syndrome, and some progress to renal failure; however, no effective therapeutic regimen has been established for this disease. We experienced a patient with LPG for whom bezafibrate treatment was very effective. This 30-year-old Japanese woman had nephrotic syndrome and type III hyperlipoproteinemia. Renal biopsy showed markedly dilated capillary lumina containing massive lipoprotein thrombi. Plasma apo E concentration was elevated to twice that of normal controls. She was proved to be a heterozygote of apo E2 Kyoto (Arg25Cys). After 2 years treatment with bezafibrate (400 mg/day), her plasma albumin gradually increased from 2.1 to 4.0 mg/dl, and intraglomerular lipoprotein thrombi disappeared almost completely. Bezafibrate decreased plasma apo E and dramatically increased high density lipoprotein (HDL)-cholesterol. The decrease in apo E was observed mainly in the pre-beta-fraction, not in the alpha fraction. Lipidological analyses of our patient suggest that the origin her lipoprotein thrombi may be mainly from pre-beta-lipoproteins and that HDL might be involved in resolving lipoprotein thrombi. Our case suggests that administration of fibrates such as bezafibrate may be a novel therapeutic strategy for resolving intraglomerular thrombi and improving nephrotic syndrome in patients with LPG.

The asymmetric chloronicotinyl insecticide, 1-[1-(6-chloro-3-pyridyl)ethyl]-2-nitroiminoimidazolidine, was prepared, and the absolute configurations of the enantiomers were determined by an X-ray analysis. The insecticidal activity against the housefly measured with metabolic inhibitors showed the (S) enantiomer to be slightly more active than the (R) isomer. Electrophysiological measurements on the American cockroach central nerve cord showed the compounds to elicite the impulses and subsequently blocked them. The neuroblocking potency of the (S) isomer was 5.9 microM, while that of the (R) isomer was as high as 73 microM. The molar concentrations required for 50% inhibition of the specific binding of [3H]imidacloprid to the housefly head membrane preparation were respectively 0.19 microM and 0.95 microM for the (S) and (R) isomers. This enatioselectivity ratio was smaller than 35 for nicotine isomers but greater than 2 for epibatidine isomers.

The Earth accretes about 30,000 tons of dust particles per year, with sizes in the range of 20-400 microm (refs 1, 2). Those particles collected at the Earth's surface--termed micrometeorites--are similar in chemistry and mineralogy to hydrated, porous meteorites, but such meteorites comprise only 2.8% of recovered falls. This large difference in relative abundances has been attributed to 'filtering' by the Earth's atmosphere, that is, the porous meteorites are considered to be so friable that they do not survive the impact with the atmosphere. Here we report shock-recovery experiments on two porous meteorites, one of which is hydrated and the other is anhydrous. The application of shock to the hydrated meteorite reduces it to minute particles and explosive expansion results upon release of the pressure, through a much broader range of pressures than for the anhydrous meteorite. Our results indicate that hydrated asteroids will produce dust particles during collisions at a much higher rate than anhydrous asteroids, which explains the different relative abundances of the hydrated material in micrometeorites and meteorites: the abundances are established before contact with the Earth's atmosphere.

Background: Although it has been recognized that women with atopic dermatitis often show menstrual-cycle-associated skin deterioration, information about this subject is meager., Objective: To clarify the clinical features of the monthly worsening of atopic dermatitis., Methods: A total of 286 Japanese women with atopic dermatitis were interviewed to see whether the menstrual cycle had any influence upon their skin lesions, and whether they had symptoms of premenstrual syndrome. Patients suffering from monthly skin deterioration were then observed during and after the monthly worsening., Results: Of the 286 patients interviewed, 134 (47%) had monthly skin deterioration, most of which occurred in the premenstrual week. There was individual difference in severity of the monthly skin worsening. All patients with the premenstrual skin aggravation had symptoms of premenstrual syndrome., Conclusions: Premenstrual worsening of skin lesions occurs in approximately half of women with atopic dermatitis. The premenstrual skin deterioration is related to the premenstrual syndrome., (Copyright 2003 S. Karger AG, Basel)

A 51-year-old woman with autoimmune pancreatitis is reported in whom treatment with ursodeoxycholic acid (UDCA) was beneficial. Complaining of epigastric discomfort, she presented with liver dysfunction of the cholestatic type, and diabetes mellitus. Pancreatic imaging revealed a diffuse swelling of the body, an irregular narrowing of the main pancreatic duct, and a terminal stricture of the common bile duct. Histologically, the biopsied pancreas was replaced by fibrous tissue with a small amount of mononuclear cell infiltration. She had anti-carbonic anhydrase-II antibody and anti-lactoferrin antibody. After treatment with UDCA, her liver dysfunction and diabetes mellitus improved and the pancreas size was reduced. Steroid therapy is usually indicated for this disorder, but UDCA may be given as an alternative choice.

The insecticidal potencies of dinotefuran and analogues against the adult male American cockroach, Periplaneta americana (L) were measured by injection with or without metabolic inhibitors. The potency of dinotefuran was close to those of clothianidin and imidacloprid under the conditions used. The nerve-excitatory and nerve-blocking activities were measured with central nerve cords of P americana. The nerve-excitatory activity of dinotefuran was lower than that of imidacloprid, but was comparable with that of clothianidin. The nerve-blocking activity of dinotefuran was comparable with that of imidacloprid and slightly higher than that of clothianidin. Quantitative analyses showed that variations in the insecticidal activity were better correlated with variations in the nerve-blocking activity than with those in the nerve-excitatory activity when the contribution of the hydrophobic factor was allowed for.

1. We investigated the effects of bepridil on the two components of the delayed rectifier K(+) current, i.e., the rapidly activating (I(Kr)) and the slowly activating (I(Ks)) currents using tight-seal whole-cell patch-clamp techniques in guinea-pig ventricular myocytes, under blockade of L-type Ca(2+) current with nitrendipine (5 microM) or D600 (1 microM). 2. Bepridil decreased I(Ks) under blockade of I(Kr) with E4031 (5 microM), in a concentration-dependent manner. The concentration-dependent inhibition of I(Ks) by bepridil was fitted by a curve, assuming one-to-one interactions between the channel and the drug molecule. The concentration of half-maximal inhibition (IC(50)) was found to be 6.2 microM. 3. The effect of bepridil on I(Kr) was assessed using an envelope-of-tails test. In the control condition, a ratio of the tail current to the time-dependent current measured during depolarization was large (>1) at shorter pulses (<200 ms), and it decreased to a steady state value of approximately 0.4 with increases in the pulse duration. Bepridil at a concentration of 2 microM did not decrease this ratio at shorter pulses. 4. In a short-pulse (duration=50 ms) experiment that largely activates I(Kr), the drug was found to block I(Kr) in a cooperative manner (Hill coefficient=3.03) and the IC(50) was 13.2 microM. 5. These results suggest that bepridil at a clinical therapeutic concentration ( approximately 2 microM) selectively blocks I(Ks) but does not inhibit I(Kr). This may relate to the characteristic frequency-dependent effects of bepridil on the action potential duration (APD), e.g., the non-reverse use-dependent prolongation of APD.

Intermittent intestinal bleeding persisted in a 77-year-old male, who had undergone grafting for abdominal aortic aneurysm. Each attack lasted for a few weeks and spontaneously resolved. Only a minute abnormality was found in the third portion of the duodenum; barium studies showed a segmental narrowing, but endoscopy disclosed only a small erosion in that portion. Massive and fatal gastrointestinal hemorrhage broke out 6 months after the onset of bleeding. Autopsy revealed an adhesion area with a small fistula formation between the duodenum and aorta. Even slight endoscopic findings should be considered suggestive of aortoenteric fistula in patients after aortic surgery.

To compare the efficacy of low and relatively high dosages of recombinant interferon (IFN)-alpha-2a in Japanese patients with chronic hepatitis C, as well as to characterize the type of patients who will respond well to a low-dosage treatment, 88 patients with histologically proven chronic hepatitis C were randomly assigned to two treatment groups; one treated with IFN-alpha-2a 6 MU daily for 2 weeks followed by 6 MU three times weekly for 22 weeks (6-MU group), and another given the same initial treatment followed by 3 MU three times weekly for 22 weeks (3-MU group). The rate of sustained normalization of ALT 6 months after the cessation of treatment was 33% in the 3-MU group and 40% in the 6-MU group (p = 0.64). In addition, there was no difference in elimination of serum HCV-RNA 6 months after the cessation of treatment between the 3-MU group (26%) and 6-MU group (29%). Multivariate stepwise regression analysis revealed that serum HCV-RNA level (p = 0.0035) and platelet count (p = 0.0009) were independent variables useful in predicting a sustained response of ALT. The sustained response rate of ALT in patients with a serum HCV-RNA level less than 10(5) copies/ml and serum platelet level above 15 x 10(4)/microliter was 71%, whereas that in patients with a serum HCV-RNA level above 10(5) copies/ml and serum platelet level less than 15 x 10(4)/microliter was 12%. These results indicate that a high rate of sustained response to IFN therapy can be expected in chronic hepatitis C patients with a low serum level of HCV-RNA and a high level of platelets, even if treated with a low dose of IFN.

We evaluated the influence of the Hanshin-Awaji earthquake on the patients in our internal medicine department. After the initial rush of patients with injury, the number of respiratory diseases, largely pneumonia, increased within one month. This same event, however, seemed to decrease attacks among asthma patients. During the following three months, the number of peptic ulcer patients increased: 39.5% had a giant gastric ulcer and 34.8% had bleeding complications. Diabetic control of outpatients became worse after the earthquake. It is important to recognize that various disorders involving physical and psychological problems develop at different stages after a large-scale disaster.

Hydrolysis of cefdinir leads to pH-dependent isomerizations and beta-lactam ring-opening. Lactam ring opened gamma-lactones were produced as a mixture of four diastereoisomers based on the lactone methyl, and C-6 isomerizations in acidic to neutral solutions. Cefdinir and its 7-epimer were hydrolyzed to clarify the pathway leading to these lactones and the mechanism of C-6 epimerization with the aid of chiral separation techniques. Chiral separation using a bovine serum albumin column was employed to detect the beta-lactam ring opened products of cefdinir and its 7-epimer; the C-6 and C-7 isomerization was thereby observed; however, it was found to be pH-dependent at pH > or = 9. Optical activity detection applied to the lactones produced from cefdinir and its 7-epimer demonstrated that the corresponding peaks of these lactones were enantiomeric pairs. In addition, the smallest rate constant at pH 4 was observed for C-6 epimerization of the lactones, and it was found to proceed without deprotonation at C-6 by 1H-NMR spectroscopy. From the results of these studies, a plausible mechanism for C-6 epimerization has been proposed. Additionally, it was confirmed that two degradation pathways were involved during hydrolysis of cefdinir to the lactone.

Hydrolytic degradation products of cefdinir were studied in acidic (pH 1), neutral (pH 6), and basic (pH 9) solutions. Seven major degradation products were isolated by preparative and/or high-performance liquid chromatography and characterized by UV, IR, 1H-NMR, and mass spectra. To clarify degradation pathways in each pH solution, kinetic and product analyses during hydrolysis of cefdinir were carried out along with the followup reaction of representative degradation products. Cefdinir was shown to degrade via two major degradation routes: beta-lactam ring-opening and pH-dependent isomerizations (lactonization, epimerization at C-6 or C-7, syn-anti isomerization of N-oxime function).

A 54-year-old man was admitted to the hospital because of the restriction of the right visual field. Goldmann's visual field test revealed the right central hemianopsia. MRI showed the infarction of the left occipital lobe tip. Cerebral angiography showed the occlusion of the left calcarine artery but no abnormality in the branches of the middle cerebral artery (MCA). The occipital lobe tip receives the projection from the macular area and is supplied by both calcarine artery and a branch of MCA. Therefore, cases of central homonymous hemianopsia due to vascular disorders have been relatively rare and the macular vision is usually spared. In contrast to the above knowledge, only one artery occlusion resulted in the central hemianopsia in our case. Poor anastomosis between PCA and MCA in the occipital tip of our patient may explain occurrence of the infarction of that area.

E-selectin is an adhesion molecule of endothelial cells that binds to cancer cells mediated by sialyl Lewis A (sLea) or sialyl Lewis X (sLex). It is suspected to be involved in hematogenous metastasis of tumors. Therefore, it is worth examining E-selectin expression in human colorectal cancer and its hepatic metastasis. In the present study, E-selectin was clearly revealed on the endothelial cells of small vessels adjacent to cancer nests in both primary and metastatic nests in immunohistochemistry. In these tissues, E-selectin was observed on the endothelial cells lining the lumen of small vessels. Its expression adjacent to cancer nests appears to be induced through some stimuli by cancer cells, since its degree of expression is inversely correlated to the distance of the blood vessels from the cancer nests (P < 0.001). Endothelial cells adjacent to the metastatic lesion expressed E-selectin more extensively than those adjacent to the primary foci. This is also in line with the finding on serum E-selectin levels which were significantly elevated in the metastatic group compared to the non-metastatic group. The serum E-selectin level may provide useful information in the diagnosis for hepatic metastasis of colorectal cancer, although the results are still very preliminary.

E-selectin is an adhesion molecule of endothelial cells that binds to cancer cells mediated by sialyl Lewis A (sLea) or sialyl Lewis X (sLe(x)). It is suspected to be involved in hematogenous metastasis of tumors. Therefore, it is worth examining E-selectin expression in human colorectal cancer and its hepatic metastasis. In the present study, E-selectin was clearly revealed on the endothelial cells of small vessels adjacent to cancer nests both in primary and in metastatic nests in immunohistochemistry. In these tissues, E-selectin was observed on the endothelial cells lining the lumen of small vessels. Its expression adjacent to cancer nests appears to be induced through some stimuli by cancer cells, since its degree of expression is inversely correlated to the distance of the blood vessels from the cancer nests (p < 0.001). Endothelial cells adjacent to the metastatic lesion expressed E-selectin more extensively than those adjacent to the primary foci. This is also in line with the finding on serum E-selectin levels which were significantly elevated in the metastatic group as compared with the non-metastatic group. The serum E-selectin level may provide useful information in the diagnosis for hepatic metastasis of colorectal cancer, although the results are still tentative.

The immunohistochemical analysis using the monoclonal antibodies to the blood group antigens was performed on the tissues of 387 colorectal cancers and 307 normal colonic tissues, and the relation between expression of these antigens and prognosis of the patients with stage 2 was also investigated. La, Le(b), and CA 19-9 were used for type 1 antigens, and Le(x), Le(y), and Sialyl Le(x) for type 2, respectively. Expression of Ca 19-9 and Silyl Le(x) remarkably increased in cancers throughout the colorectum. Le(b) and Le(y) were expressed in only 0-17% of the normal distal colon, but in almost colonic tumors. Therefore CA 19-9 and Sialyl Le(x) are tumor-associated antigens in the whole colorectum, and Leb and Le(y) in the distal colon. Expression of CA 19-9 in primary tumor provided more prognostic information and risk of liver metastasis than other Lewis blood group antigens.

A trial of FP therapy, a novel systemic chemotherapy consisting of 5-FU and low-dose CDDP, was carried out in patients with advanced gastric cancer and the clinical effects were evaluated. Five hundred mg/body/day of 5-FU was continuously administered via the central venous catheter for 7 consecutive days and 10mg/day of CDDP was rapidly administered with 500ml saline on days 1-5. The regimen was repeated for at least 4 weeks. The FP therapy was carried out in 22 cases, including several patients who underwent FP as an adjuvant therapy; 1 CR, 2PR's 1MR and 2NC's were obtained among the 6 patients with clinically evaluable lesions, resulting in a response rate of 50%. In four cases, the FP therapy was given as a neoadjuvant therapy, and histopathological examination of the resected specimen revealed histological effects exceeding Grade 2 in all 4 cases. Bone marrow suppression was the most commonly observed side effect, but renal dysfunction and nausea were not found. FP therapy is considered an effective therapy against advanced gastric cancer, from the viewpoint of both the clinical and adverse effects, in comparison with conventional regimen consisting of 5-FU and a single and large dose of CDDP.

In this study, 1500AA, an activated charcoal with a strong affinity for the lymphatic system, was examined for its ability to deliver chemotherapy to metastatic lymph nodes. First, the anticancer effect on metastatic lymph nodes was assessed in an experiment using the mouse mammary tumor, MM48. Pathological examination of the inguinal lymph nodes revealed a metastatic rate of 50% in the group given cisplatin (CDDP)-saline, but 20% in the group given CDDP-charcoal. Next, in a canine model, CDDP dissolved in normal saline was administered directly into the mediastinum, and CDDP was given with fine particles of activated charcoal in the same manner in the other group. The concentration of CDDP in the lymph nodes and the plasma rapidly increased to peak in 10 min in the CDDP-saline group, whereas it increased slowly to peak in 20-30 min in the CDDP-charcoal group. Moreover, the CDDP-charcoal group was found to have a much higher concentration of CDDP in the lymph nodes than the CDDP-saline group.

We present herein the case of a patient with actinomycosis involving the pelvic cavity, who presented with a rectal stricture. It is rare for this type of actinomycosis to be accurately diagnosed preoperatively, but a precise diagnosis, made using needle biopsy guided by computed tomography allowed for successful treatment by resection of the granulation tissue surrounding the rectal stricture through a transsacral approach.

The immunohistochemical analysis using the monoclonal antibodies to the blood group associated antigens Lea, Leb, CA19-9, and CEA, were performed on the tissues of the colorectal cancers, adenomas, normal mucosae and distant metastatic lesions, to determine whether the given degree of expression have some relation to the prognosis of patients or the potential of metastasis. We also analysed the serum levels of CA19-9 and CEA by RIA and compared them with the results of immunopathology. The more pronounced expression of CEA, Lea, Leb, and CA19-9 was observed in proportion to the progress of the cancer. In those cases of immunohistochemically Lea negative results in tissues, CA19-9 was not detected either in the serum level nor in tissue sections, therefore all cases of Lea negative results were eliminated in the evaluation of the clinical significance of CA19-9. Positive expression of CA19-9 in tissue of cancer indicated a poor prognosis of the patient and high risk of distant metastasis. Higher intensity of staining was observed in hepatic metastasis, in comparison with the primary lesion. These studies demonstrated that immunohistochemical analysis of CA19-9 and blood group antigens in useful tool for evaluation of prognosis and risk of metastasis in colorectal cancer.

Targeting chemotherapy to the metastatic lesions of the lymph nodes after surgical removal of the main tumor, a drug delivery system using ultrafine particles of activated charcoal was developed and examined for its ability to adsorb mitomycin C (MMC) and to transport MMC to the lymph system. Satisfactory results were obtained. In animal experiments, serial sampling of thoracic duct lymph by cannulation and serial samplings of peripheral vein blood after injection of MMC-charcoal solution into the subserosal space of the intestinal wall were made to study the pharmacodynamics of the lymph-blood system through analysis of MMC regression curves. Clearance (K) and half-life (t1/2) are calculated from the formula; C(t) = C(t0) X e-kt, and compared with that of MMC-saline. Activated charcoal has a proven ability to transport MMC to the lymphatic system. With activated charcoal, MMC is retained for much longer in the lymph nodes than with saline. Congestion of the lymph system was produced by ligation of the thoracic duct in CH-40, with 25% prolongation of t1/2. In conclusion, these drug delivery systems are suitable for targeting chemotherapy at lymph node metastases, and it is proven that 1500 AA Mitsubishi ultrafine charcoal is a good carrier of drug and a slow drug-release material in the lymphatics. Minimal side effects are expected because of the constant low concentrations in the general circulation.

Two hundred fifty-five patients with colo-rectal carcinoma underwent operations in our department between January 1980 and December 1988. The five-year survival rate of stage IV patients (30 cases) was 58%, and the three-year survival rate of stage V patients (44 cases) was 8%. The study for the expression of blood group-related cancer-associated antigens (Lea, CA19-9, etc.) in colo-rectal cancers using immunohistological method and a series of mouse monoclonal antibodies revealed that the stromal staining pattern of CA19-9 means high malignancy with poor prognosis. Nineteen patients with locally invading rectal cancer were submitted to total pelvic exenteration with urinary diversion. The operative mortality rate was 5.3%. A determinate 5-year survival rate of 4.5 was achieved. Fourteen patients with local recurrent lesions of rectal cancer following abdominoperineal resection were submitted to pelvic exenteration combined with sacral resection. Two patients are alive disease free for longer than four years at this writing. This operation assures a better quality of life, lessening of symptoms, disease control and, in selected patients, a cure.