Men who were thin during early adulthood exhibited greater weight gain-associated visceral fat accumulation in a study of middle-aged Japanese men.

OBJECTIVE: This study aimed to assess the relationship between weight gain from early adulthood and visceral fat accumulation. METHODS: The participants were 549 men aged 42 to 64 years who were randomly selected from the local resident registry for the National Institute for Longevity Sciences' neighbourhood. They were asked to recall their weight at 18 years of age, and then, post-18 weight-change values were calculated for each participant (their current weight minus their weight at 18). The participants were divided according to their median body mass index (BMI) at 18 years of age (initial BMI) (<20.14 and ≥20.14 kg m-2). Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured on computed tomography scans. RESULTS: The participants with initial BMI of <20.14 kg m-2 exhibited greater post-18 weight changes than those with initial BMI of ≥20.14 kg m-2. The participants' post-18 weight-change values were negatively correlated with their initial BMI and positively correlated with both VFA and SFA. The slope of the regression line for the relationship between post-18 weight change and VFA was steeper in the participants with initial BMI of <20.14 kg m-2 (ß = 4.36) than in those with initial BMI of ≥20.14 kg m-2 (ß = 3.23). CONCLUSIONS: Visceral fat accumulation is affected not only by an individual's post-18 weight gain but also by their initial BMI. Men who were thin in early adulthood experienced greater weight gain-associated VFA increases, but the same was not true for SFA.

Bipolar pulse generator for intense pulsed ion beam accelerator.

A new type of pulsed ion beam accelerator named "bipolar pulse accelerator" (BPA) has been proposed in order to improve the purity of intense pulsed ion beams. To confirm the principle of the BPA, we developed a bipolar pulse generator for the bipolar pulse experiment, which consists of a Marx generator and a pulse forming line (PFL) with a rail gap switch on its end. In this article, we report the first experimental result of the bipolar pulse and evaluate the electrical characteristics of the bipolar pulse generator. When the bipolar pulse generator was operated at 70% of the full charge condition of the PFL, the bipolar pulse with the first (-138 kV, 72 ns) and the second pulse (+130 kV, 70 ns) was successfully obtained. The evaluation of the electrical characteristics indicates that the developed generator can produce the bipolar pulse with fast rise time and sharp reversing time.

Intrathecal chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea encapsulated into hybrid liposomes for meningeal gliomatosis: an experimental study.

1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), one of the chloroethyl nitrosoureas, is effective against malignant glioma. To develop its use in intrathecal chemotherapy, we encapsulated BCNU in hybrid liposomes composed of dimyristoylphosphatidylcholine and micellar surfactants (Tween 20) and dissolved it in artificial cerebrospinal fluid (lipo-BCNU). We then studied the toxicity of hybrid liposomes and cellular proliferation inhibition of lipo-BCNU in vitro. We found that 3 mM hybrid liposomes did not affect the viability of human endothelial cells and that lipo-BCNU inhibited the proliferation of human glioma cell lines U-105MG, U-251MG, and U-373MG, and rat glioma cell lines C6 and 9L in a concentration-dependent fashion. Wistar rats that were administered lipo-BCNU intracisternally showed no weight loss, neurological symptoms, or histological changes of the brain and spinal cord. A Wistar rat model of meningeal gliomatosis was established by intracisternal inoculation of 0.1 ml cell suspension containing 1 x 10(6) or 5 x 10(6) viable C6 glioma cells. Two days after inoculation, lipo-BCNU (BCNU, 2.5 mg/kg) was administered intracisternally. When 1 x 10(6) glioma cells were inoculated (experiments 1 and 2), the median survival times were 24.5 and 26 days in the control groups and 32 and 45 days in the lipo-BCNU-treated groups. respectively. When 5 x 10(6) glioma cells were inoculated (experiments 3-6), the median survival times were 17-29.5 days in the control groups and 23-44 days in the treated groups, respectively. Significantly prolonged survival was obtained in three of six experimental groups. After the administration of 1 ml lipo-BCNU (BCNU, 4.67 mM) or 1 ml BCNU solubilized with 5% dextrose/water (BCNU, 4.67 mM) into the cisterna magna of dogs, the cisterna magna cerebrospinal fluid was sampled, and the BCNU concentrations were assayed by high-performance liquid chromatography. The half-life of the lipo-BCNU was longer than that of BCNU solubilized with 5% dextrose/water. These results suggest that the intrathecal administration of lipo-BCNU may be possible for the treatment of meningeal gliomatosis.

High-efficiency in vivo gene transfer using intraarterial plasmid DNA injection following in vivo electroporation.

A novel method for high-efficiency and region- controlled in vivo gene transfer was developed by combining in vivo electroporation and intraarterial plasmid DNA injection. A mammalian expression plasmid for the Escherichia coli lacZ gene (driven with a SV40 early promoter) was injected into the internal carotid artery of rats whose brain tumors (from prior inoculation) had been electroporated between two electrodes. The lacZ gene was efficiently transferred and expressed in the tumor cell 3 days after plasmid injection. However, neither any gene transfers nor any elevated lacZ activity was detected in tissues outside the electrodes. The plasmid was not transferred without electroporation. Human monocyte chemoattractant protein-1 cDNA was also transferred by this method, and its long-lasting (3 weeks) expression was confirmed by using the Epstein-Barr virus episomal replicon system. The expressed monocyte chemoattractant protein-1 protein was functional, as evident by the presence of a large number of monocytes in tumor tissue. This method, electrogene therapy, which does not require viral genes or particles, allows genes to be transferred and expressed in desired organs or tissues, and it may lead to the development of a new type of highly effective gene therapy.

Effects of single and long-term administration of wheat albumin on blood glucose control: randomized controlled clinical trials.

OBJECTIVE: To examine the effects of single and long-term administration of wheat albumin (WA) on blood glucose levels and blood glucose control, respectively. DESIGN: Randomly arranged crossover trial for single administration in healthy subjects and double-blinded randomized controlled trial for long-term administration (3 months) in diabetic patients. In vitro alpha-amylase inhibitory activity of WA was also determined. SETTING: Central Research Laboratories of Nisshin Flour Milling Co. Ltd. (Saitama, Japan) for single administration and Aiwa Clinic (Saitama, Japan) for long-term administration. SUBJECTS: A total of 12 healthy adult male volunteers for the single administration and 24 type II outpatient diabetics with mild hyperglycemia for the long-term administration. INTERVENTIONS: Subjects took soups containing 0, 0.25, 0.5, and 1.0 g WA before test meals for single administration, and patients took soups with or without 0.5 g WA before every meal for the long-term (3 months) administration. RESULTS: In vitro alpha-amylase inhibitory activity of WA was 150 times that of wheat flour. In the single administration experiment, WA suppressed peak postprandial blood glucose levels in a dose-dependent manner: 31, 47, and 50% reduction after 0.25, 0.5, and 1.0 g administrations, respectively. In the long-term administration, 0.5 g of WA did not affect fasting blood glucose levels, whereas it reduced hemoglobin A1c levels. No significant adverse effects such as hypoglycemia or gastrointestinal disturbances were observed in the two experiments. CONCLUSION: In the treatment of type II diabetic patients, WA might be a useful functional food, which, with diet and exercise, could help to improve blood glucose control without any critical adverse effects.

Neurofibromatosis 2 gene has novel alternative splicings which controls intracellular protein binding.

Three novel isoforms of the neurofibromatosis 2 (NF2) gene transcripts generated from alternative splicing were identified from normal human brain, schwannoma and glioma tissues. The 3 novel transcripts lack exon 2, exons 2 and 3, exons 2-4, respectively. Recombinant isoform proteins encoded by those new transcripts have lost the previously reported ability to bind S-35-methionine labeled cellular proteins. Two of seven glioblastoma tissues expressed significantly high levels of the shorter transcripts whereas low grade astrocytomas expressed levels similar to those found in normal brain, suggesting that genomic mutation or aberrant alternative splicing of the NF2 gene may contribute to the progression of malignant gliomas.

Incidence of subacute sclerosing panencephalitis following measles and measles vaccination in Japan.

The Japanese Committee for the National Registry of Subacute Sclerosing Panencephalitis (SSPE) confirmed that 215 cases of SSPE occurred in the 20 years from 1966 to 1985, as discovered in the 10-year surveillance from April 1976 through March 1986. The annual incidence in recent years has been between 10 and 23 cases. Among cases with a certain history of measles illness or measles vaccination, 184 (90.2%) had a history of measles illness without receiving measles vaccine. There were 11 probable measles vaccine-associated cases (5.4%), three (1.5%) being vaccinated with a combined use of killed and live vaccine and eight (3.9%) with further attenuated live vaccine. There were nine cases (4.4%) without a history of either measles illness or measles vaccination. Intervals between measles illness and the onset of SSPE varied from 1 to 16 years (mean, 7.0 years). The periods following measles vaccination with further attenuated live vaccine were 2 to 11 years (mean, 4.6 years). Annual incidence rates of SSPE per million cases of measles ranged between 6.1 and 40.9 (mean, 16.1) in the 10 measles epidemic years 1968-1977, and those following vaccination with further attenuated live vaccine were zero in most years and at the highest 3.08 (mean, 0.9) per million doses of distributed vaccine.

Abnormal origin of bilateral ophthalmic arteries. Case report.

The case of a 64-year-old woman with multiple intracranial aneurysms and abnormal ophthalmic arteries arising from the bifurcation of the internal carotid artery is described. It is believed that this type of anomaly of the ophthalmic artery has not previously been reported. The neuroradiological and operative findings of this case are presented.

Enzymatic conversion of aclacinomycin A to Y by a specific oxidoreductase in Streptomyces.

A specific oxidoreductase converting aclacinomycin A to a new analog, aclacinomycin Y, was purified to apparent homogeneity from the culture filtrate of aclacinomycin-producing microorganisms. The isolated enzyme was a weakly acidic protein (isoelectric point, 5.9) with a molecular weight of about 72,000. The enzymatic reaction requires molecular oxygen and has a pH optimum at 5.5. The enzyme catalyzed an oxidation of the terminal sugar, L-cinerulose, of the trisaccharide moiety of aclacinomycin A to L-aculose (2,3,6-trideoxyhex-2-enopyranos-4-ulose) with removal of two electrons. Studies of substrate specificity revealed that the enzyme is an oxidoreductase capable of modifying anthracyclic triglycosides by oxidizing their terminal sugars.

Antitumor anthracycline antibiotics, aclacinomycin A and analogues. I. Taxonomy, production, isolation and physicochemical properties.

Aclacinomycin A and B, two major components of a new antitumor antibiotic complex, and their 19 analogues were produced by a culture of strain No. MA144-M1, which was identified as Streptomyces galilaeus. They were isolated by chelation with copper ion and silicic acid chromatography, and characterized by physicochemical methods in the anthracycline group of antibiotics.

Suprasellar hemangioblastoma in a patient with von Hippel-Lindau disease confirmed by germline mutation study: case report and review of the literature.

BACKGROUND: Hemangioblastoma (HBL) in the suprasellar region is extremely rare. CASE DESCRIPTION: A suprasellar mass was found in a 33-year-old woman with retinal HBL and bilateral adrenal pheochromocytomas. The diagnosis of von Hippel-Lindau (VHL) disease was confirmed preoperatively not only by these clinical manifestations but also by germline mutation study. The existence of VHL disease indicated a diagnosis of HBL for the suprasellar mass. The results of our mutation study indicated that this patient had type II VHL disease, suggesting that careful follow-up is essential for the early detection of renal cell carcinoma, which is often associated with type II VHL disease. Here, we summarize the previously reported features of sellar and suprasellar HBLs. CONCLUSIONS: HBLs in this region may be one manifestation of VHL disease. Genetic testing of the VHL gene of our patient could provide useful information to determine appropriate medical care and management.

Hyperreactivity of lymphocytes to streptolysin O and lack of plasma inhibitory factor (s) in patients with mucocutaneous lymphnode syndrome.

Lymphocyte activation by streptolysin O (SLO) and factors in the plasma which inhibit the response to SLO were examined in 19 patients with mucocutaneous lymphnode syndrome (MCLS), 54 age-matched (6 months-6 years) normal children, 41 normal children older than 6 years and 10 normal adults. In normal children younger than 6 years, the response to SLO was weak and in many cases no response was seen. On the other hand, in the patients with MCLS, the response of lymphocytes to SLO was high and comparable to the response in adults and children older than 6 years. The DNA synthesis of lymphocytes stimulated by SLO was inhibited almost completely by autologous or allogeneic plasma of many of the normal children and adults. The plasma of patients with MCLS did not inhibit, but rather enhanced the response to SLO. These results suggest that the increased response of lymphocytes to SLO and the lack of plasma inhibitory factors in patients with MCLS may be due to the immune response to the pathogen of MCLS, as yet undiscovered.

Cell-mediated cytotoxicity-supporting activity of various human gammaglobulin preparations.

Antibody activity, especially that involved in the reaction of antibody-dependent cell-mediated cytotoxicity (ADCC), of five commercially available human gammaglobulin preparations (standard, pepsin-treated, plasmin-treated, polyethylene glycol-fractionated and S-sulfonated gammaglobulin) was measured. All these gammaglobulin preparations had high titers of hemagglutination inhibition and neutralizing antibody against measles virus. In ADCC reaction, the pepsin-treated gammaglobulin preparation showed no antibody activity. The standard gammaglobulin preparation showed weak activity only when highly diluted. The remaining three preparations showed high activity. Though the S-sulfonated gammaglobulin preparation showed no activity in ADCC reaction, it showed high activity after reconversion by means of oxidation and reduction in vitro. The plasmin-treated gammaglobulin preparation showed greater activity than the polyethylene glycol-fractionated preparation of the optimal concentration. In ADCC tests using the plasmin-treated gammaglobulin preparation, K cell activity was strongly inhibited by Hg (thimerosal), while, in those using the standard gammaglobulin preparation, the activity was hardly influenced by Hg, suggesting that the low ADCC activity of the standard gammaglobulin preparation of high concentrations was due to the inhibitory effect of aggregated immunoglobulin G molecules.

[Cefuzonam, a new cephem antibiotic in the field of pediatrics. Concentrations in serum and clinical efficacy].

A new cephem antibiotic, cefuzonam (L-105, CZON) was studied for its concentrations in serum and clinical efficacy in the field of pediatrics. To examine the concentration of CZON in serum, 20 mg/kg of CZON was administered by intravenous drip infusion to a male patient of 6 years and 7 months. The half-life of the drug in serum was 0.97 hour after administration. CZON was administered to 7 cases of pediatric infections, and clinical result were "excellent" in 4, "good" in 1, "poor" in 2: the efficacy rate was 71.4% or 5 cases out of 7. As an adverse reaction, eruption was observed in 1 patient.

[Fundamental and clinical studies on cefixime in pediatrics].

We have evaluated cefixime (CFIX) fine granules for pharmacokinetics and therapeutic effectiveness in children with infections. The results were summarized as follows. Pharmacokinetic parameters after the oral administration of single doses of 1.5 mg and 6.0 mg per kg body weight in a cross-over design in 1 child were as follows: The peak serum CFIX concentrations were 0.65 microgram/ml at 2 to 3 hours and 3.33 micrograms/ml at 4 hours for the low and the high doses, respectively; the respective biological half-lives were 2.4 hours and 2.5 hours, and urinary recovery was 10.3% at 8 hours and 5.2% at 12 hours, respectively. A clinical study was performed on 19 children with infections, including 7 with bronchitis; 3 each with tonsillitis, UTI, and cervical lymphadenitis; and 1 each with pharyngitis, retroauricular lymphadenitis, and enteritis. Doses ranging from 1.8 to 7.8 mg/kg body weight were given b.i.d. or t.i.d. The period of treatment ranged from 3 to 13 days. The therapeutic response was considered "excellent" in 15 and "good" in 4, with an effectiveness rate of 100%. No side effects were observed. The only abnormal laboratory findings was a slight elevation of GOT and GTP recorded in 1 child. It was concluded that CFIX was a promising drug for the treatment of bacterial infections in children.

[Clinical effect of ceftizoxime suppositories].

The therapeutic effect of ceftizoxime suppositories (CZX-S) was studied in 8 physically handicapped patients, comprising 6 with pharyngitis, 1 with pneumonia, and 1 with urinary tract infection. The clinical effect was "excellent" in 7 and "good" in 1. Neither adverse reactions nor abnormal laboratory test findings attributable to CZX-S were detected. CZX-S proved to be useful in physically handicapped children, especially in those not suited to treatment with oral or intravenous preparations.

[Therapeutic effects of cefmenoxime in the treatment of various infections on infants and children].

The therapeutic effects of cefmenoxime (CMX), a new synthetic cephalosporin antibiotic, were examined in the treatment of various pediatric infections. Patients treated were infants and children ranging from one-month-old to 13-year-old suffering from pharyngitis in 2 cases, bronchopneumonia in 3 cases, cervical lymphadenitis in 2 cases, urinary tract infections in 7 cases, tympanitis in 2 cases, suppurative meningitis, sepsis, subcutaneous apostem, acute enteritis, chest wall apostem, phlegmon, staphylococcal scalded skin syndrome in 1 case each, a total of 23 cases. As regards method of administration, CMX from a vial was dissolved in physiological saline or distilled water for injection, and the solution was administered by 3 to 5 minutes one short intravenous injection (14 cases), or CMX was diluted with large volume parenteral product and administered by 30 to 60 minutes drip infusion (9 cases). The dosage of the drug was 30 to 200 mg/kg/day; 103 mg/kg/day and under in 21 cases, 150 mg/kg/day and 200 mg/kg/day in 1 case each. The administration was continued for 3 to 27 days. As regards clinical efficacy, "good" or "excellent" results were obtained in all the cases except 2 cases, one was alpha-Streptococcus acute tympanitis supervening neuroblastoma, and the other was Pseudomonas urinary tract infection. The efficacy rate was 91.3% with excellent in 11 cases, good in 10 cases. As regards bacteriological effects, of 13 strains of Gram-positive bacteria, 10 strains were eliminated and 3 strains were not changed, while of 10 strains of Gram-negative bacteria, 8 strains were eliminated and 2 strains were reduced; thus CMX showed better results against Gram-negative bacteria rather than against Gram-positive ones. The antimicrobial activity of CMX against Gram-positive bacteria was inferior to those of CTM and CEZ, but CMX showed the highest antimicrobial activity against Gram-negative bacteria. No clinical side effects nor abnormal laboratory findings obviously attributable to CMX were observed.

[Therapeutic effects of cefoxitin in the treatment of various infections in children (author's transl)].

In order to ascertain the therapeutic effects of cefoxitin (CFX), a new semisynthetic cephamycin antibiotic, it was administered to pediatric patients with several infections. There were 8 patients with acute respiratory disease (ARD), 3 with urinary tract infection (UTI), 2 with appendicitis complicated with peritonitis, 2 with scarlet fever, one each of left coxitis, infected medial cervical cyst, febrile illness after a V-P shunt operation, purulent parotitis and intractable diarrhea with fever, namely, a total of 20 patients aged from one month to 11 years 6 months. A CFX vial which contained 1 g of CFX was used in two ways, i.e., one shot intravenous injection and drip infusion. The dosage of the drug varied from 57 to 121 mg/kg/day and the administration was continued from 2 to 20 days. Clinical effects were evaluated as follows: when cardinal symptoms disappeared within 3 days it was considered to be 'excellent'; within 5 days 'good'; and no change of clinical symptoms within 5 days 'poor'. The bacteriological effect was expressed as 'eliminated', 'unchanged' and 'undetermined'. Clinical efficacy evaluated as 'excellent' occurred in 11 cases, 'good' in 8 cases and 'poor' in 1 case, the efficacy rate being 95.0%. When classified by the disease, the efficacy rate was as follows: 'good' to 'excellent' in 7 out of the 8 cases of ARD, 'excellent' in all of the 3 cases of UTI, 'good' and 'excellent' in the 2 cases of scarlet fever and in the 2 cases of peritonitis, 'excellent' in each case of left coxitis, purulent parotitis and intractable diarrhea with fever, 'good' in each case of infected medial cervical cyst and febrile illness with a V-P shunt operation. From the bacteriological point of view, 'eliminated' occurred in 5 cases, 'reduced' in 1 case and 'undetermined' in the 2 cases of ARD, 'eliminated' in all of the 3 cases of UTI, 'eliminated' in 1 case and 'undetermined' in the 1 case of peritonitis, 'undetermined' in the 2 cases of scarlet fever, 'eliminated' in each case of infected medial cervical cyst and purulent parotitis and 'undetermined' in the other cases. Antimicrobial efficacy measured by MIC was compared with CEZ and CET, and the results were as follows: CFX was inferior to the two cephalosporins for S. aureus, it was between CEZ and CET for H. influenzae and H. parainfluenzae, and CFX was superior to CEZ and CET for E. coli. All of the 3 antibiotics had poor antimicrobial efficacy for P. aeruginosa and S. faecalis. There were neither clinical side effects nor abnormal laboratory findings which were obviously attributable to CFX during and after administration of the drug.

[The therapeutic effects of aspoxicillin on various infectious diseases in children].

Clinical application to ascertain the effects of aspoxicillin (ASPC), a new semisynthetic penicillin antibiotic, upon several infectious diseases of children was performed in 7 cases with pneumonia, 5 cases with acute bronchitis, each case with tonsillitis, enterocolitis, urinary tract infection and suspected sepsis. ASPC was injected by drip infusion and the dosage was 63-117 mg/kg/day in 3 and 4 times a day. Clinical efficacy obtained as "excellent" was in 7 cases, "good" in 8 cases "poor" in 1 case, and efficacy rate was 93.8%. From the bacteriological point of view, eliminated in each of H. influenzae, H. parainfluenzae, group A beta-Streptococcus and unchanged in a case of E. coli. There were transient thrombocytopenia in 2 cases and eosinophilia in 3 cases.

[Clinical evaluation of aztreonam against pediatric purulent meningitis].

A monotherapy of aztreonam (AZT) was applied to 9 male and 3 female pediatric patients of ages ranging from 2 months to 8 years and 11 months with serious purulent meningitis. The results are summarized as follows: 1. Daily dosages of 134 to 400 mg/kg were given 3 to 4 times a day for 10 to 28 days. 2. The isolated pathogens were Neisseria meningitidis in 2 cases, Escherichia coli in 3 cases, Haemophilus influenzae in 6 cases, but the pathogen of the last case was unknown. In this case, the patient had myelomeningocele and suffered from recurrent purulent meningitis. 3. Clinical effect was "excellent" in 5 of 12 cases, "good" in 7 cases and efficacy rate was 100%. Microbiological tests were performed on 9 cases during the course of treatment and bacterial elimination rate was 100%. All the pathogens were eliminated in 72 hours. 4. One case of diarrhea was observed, but the diarrhea started before the administration of AZT and was stopped after the AZT treatment. A slight elevation of GOT value was observed in 1 case but the value returned to the initial level promptly after the treatment was completed. It is considered that AZT is highly useful for purulent meningitis caused by Gram-negative pathogens such as H. influenzae, E. coli and N. meningitidis.