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Biomedical subjects

M Baba

Publications and source records attributed to M Baba.

At least 109 records · Page 6Linked to original sources

Highly potent and selective inhibition of human immunodeficiency virus type 1 by a novel series of 6-substituted acyclouridine derivatives.

In the search for novel derivatives of 1-[2-(hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT), we have found that several 5-ethyl-6-(3,5-dimethylphenylthio)uracil and 5-ethyl-6-(3,5-dimethylbenzyl)uracil analogues are exquisitely potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in a variety of cell culture systems. Of this series, 5-ethyl-1-ethoxymethyl-6-(3,5-dimethylbenzyl)uracil (E-EBU-dM) emerged as the most active congener. Its 50% inhibitory concentration for HIV-1 (HTLV-IIIB) in MT-4 cells and peripheral blood lymphocytes is 2.2 and 0.45 nM, respectively. These concentrations are more than 10(5)-fold lower than the 50% cytotoxic concentrations of E-EBU-dM for the host cells. All compounds proved equally inhibitory to a number of clinical HIV-1 isolates, including a 3'-azido-2',3'-dideoxythymidine-resistant variant. However, as previously noted for HEPT, they do not inhibit human immunodeficiency virus type 2 replication. Reverse transcriptase assays have revealed that these HEPT derivatives act specifically on HIV-1 reverse transcriptase, according to a mechanism that is different from that of the dideoxynucleosides.

Antiviral Agents

Novel naphthalenedisulfonic acid anti-HIV-1 agents. Synthesis and activity against reverse transcriptase, virus replication and syncytia formation.

Several naphthalenedisulfonic acid derivatives have been synthesized and evaluated in four anti-HIV-1 screens. Antiviral activity was evaluated in the assays that measure inhibition of HIV-1 reverse transcriptase (RT), HIV-1 induced giant cell (syncytia) formation, and HIV-1 induced cytopathogenicity in both a laboratory and clinical strain of HIV-1. 4-acetylamino-5-hydroxy-2,7- naphthalenedisulfonic and a bis naphthalenedisulfonic acid derivative emerged as the most active compounds exhibiting activity in all assays at concentrations non-toxic to the host cells. The bis 3-amino-1,5-naphthalenedisulfonic acid derivative was the most active compound, but less active than the bis 4-amino-5-hydroxynaphthalenedisulfonic acid analog in the assays that measure RT and syncytia inhibition. However, in the assay that measured inhibition of cytopathogenicity in a clinical HIV-1 isolate, 4-acetylamino-5-hydroxy-2,7-naphthalenedisulfonic acid was the most potent analog, demonstrating an in vitro therapeutic index greater than 54. This study shows that for certain naphthalenedisulfonic acid moieties a bis derivative is not a requirement for significant anti-HIV-1 activity. These agents represent a new class of lead non-nucleoside anti-HIV-1 compounds worthy of further development for potential anti-AIDS therapy.

Acquired Immunodeficiency Syndrome

[A community-based education program for serum cholesterol reduction in urban hypercholesterolemic persons--comparison of intensive and usual education groups].

A community-based education program was conducted for persons found to be hypercholesterolemic by screening during cardiovascular surveys, in an urban population, to evaluate the feasibility and effect of the program in primary prevention of coronary heart disease. The subjects were men and women aged 40-64 living in the suburbs of Osaka whose serum total cholesterol was between 240 and 299 mg/dl in both the 1988 and the 1989 surveys. Persons with hypothyroidism, those taking medication for hypercholesterolemia or hypertension, and with a history of stroke and coronary heart disease were excluded. Of the 111 persons who were eligible, 104 persons were recruited for the program on March, 1989. The 104 persons were randomly assigned to either an intensive education group (n = 51) or a usual education group (n = 53). For the intensive education group, seven education classes were held from April to November, 1989. Lectures, practice sessions, interviews, and spot cholesterol measurements were conducted in a local community center. The usual education group received a letter with results from the 1989 survey and dietary instruction in April 1989 and an education class in September 1989. Mean serum cholesterol in the intensive education group showed a 10.0 mg/dl greater reduction in September 1989 and a 9.0 mg/dl greater reduction in March 1990 than in the usual education group (p less than 0.05) while mean HDL-cholesterol did not change in either groups. The intensive education group reported a larger decrease in the dietary frequency of chicken egg, poultry skin and small fishes, foods which are rich in saturated fat and cholesterol. The frequency of fatty meat, butter and fish eggs was low in both groups and did not differ between the two groups after the one-year program. These results indicate that a population-based education program is feasible and effective in reducing serum total cholesterol of hypercholesterolemic persons.

Adult

[A case of Ramsey Hunt syndrome with multiple cranial nerve paralysis and acute respiratory failure].

The authors report a 56-year-old woman with Ramsey Hunt syndrome with multiple cranial nerve paralysis and acute respiratory failure. Five days before admission, she experienced right otalgia and right facial pain and consulted an otolaryngologist of our hospital, who diagnosed the illness as acute parotitis and laryngopharyngitis. One day before admission, she experienced mild dyspnea and general fatigue and came to our hospital emergency room. A chest X-ray film revealed no abnormalities but some blisters were observed around her right ear. The next day, her dyspnea became more severe and she was admitted. A chest X-ray film on admission revealed right lower lobe consolidation, and neurological examination disclosed multiple cranial nerve paralysis, i.e., paralysis of the right fifth, seventh, eighth, ninth, tenth, eleventh, twelfth and left tenth cranial nerve. The serum titer of anti-herpes zoster antibody was elevated to 1,024, and the patient was diagnosed as having Ramsey Hunt syndrome with multiple cranial nerve paralysis. Arterial blood gas analysis revealed hypoxemia with hypercapnea, which was considered to be due to aspiration pneumonia and central airway obstruction caused by vocal cord paralysis. Mechanical ventilation was soon instituted and several antibiotics and acyclovir were administered intravenously, with marked effects. Three months after admission, the patient was discharged with no sequelae except mild hoarseness. Patients with herpes zoster oticus, facial nerve paralysis and auditory symptoms are diagnosed as having Ramsey Hunt syndrome. This case was complicated by lower cranial nerve paralysis and acute respiratory failure, which is very rare.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

[A clinicopathological study of thymomas, with special reference to evaluation of malignant grade by morphometric analysis].

To determine the factors influencing the extent and recurrence of thymoma, 31 cases of thymoma who had undergone complete resection were analyzed clinicopathologically with special reference to the nuclear area of epithelial cells. The mean tumor size and incidence of recurrence of stage III thymomas were significantly larger and higher than those of stage I thymomas. The nuclear area of epithelial cells of stage III thymomas (72.9 +/- 29.2 micron 2) was significantly larger than that of stage I thymomas (48.4 +/- 13.2 micron 2) or stage II thymomas (49.4 +/- 11.6 micron 2). The nuclear area of thymomas with recurrence (70.2 +/- 21.5 micron 2) was significantly larger than that of those without recurrence (50.2 +/- 12.8 micron 2). In 16 cases who were followed up for 5 years or more, the nuclear areas were over 50 micron 2 in all thymomas with recurrence, while in 8 of 11 thymomas without recurrence it was under 50 microns 2. These results indicated that the tumor size and nuclear area increased step-wisely in association with the advance of clinical stage and that the incidence of recurrence was related to not only clinical stage but also nuclear area. Thymomas with large nuclear area (over 50 microns 2) are considered to be a high-risk group of recurrence and should be carefully followed up.

Adult

[Deformation of brain and stress distribution caused by putaminal hemorrhage--numerical computer simulation by finite element method].

Deformation and stress distribution caused by putaminal hemorrhage in two-dimensional model brain were analyzed by computer simulation using finite element method. The model brain was composed of cerebral cortex, white matter, caudate nucleus, lenticular nucleus, thalamus and lateral ventricle. Young's modulus of gray and white matter was assumed to be 0.08 and 0.04 kgf/cm2, respectively, and Poisson's ratio was 0.47 for both of them. Bleeding of 100 mmHg pressure was represented by 4 vectors of force directing anterior, lateral, posterior and medial direction from the middle portion of putamen. Calculation of finite element method was carried out by a 16-bit personal computer. The calculated deformation of brain presented a hematoma cavity elongated from anterior to posterior direction at the lenticular nucleus. Mass effect of hematoma was noted from displacement of the anterior horn of the lateral ventricle and the internal capsule. Distribution of stress vector revealed the stress concentration at the lenticular nucleus while small stress was noted all over the model brain. Strength of principal stress was presented by contour-line and took the shape of concentric circles with a center at the putamen. This study suggested that the computer simulation by finite element method would be a useful technique to analyze the physical phenomenon of brain suffered from intracerebral hemorrhage.

Basal Ganglia Diseases

[Mechanism of F-wave conduction delay in acute Guillain-Barré syndrome].

We measured M-wave and F-wave conduction time between the wrist and the elbow in 16 median nerves of acute phase of Guillain-Barré syndrome. Studies were carried out within 14 days after the onset of the weakness. In 20 healthy subjects, conduction times of M- and F-waves were almost similar, while F-wave conduction time was longer than the corresponding M-wave conduction time in the acute phase of the illness. This dissociation between the F-wave and the M-wave conduction time was exaggerated when the minimal F-latency was longer. The results suggest that an F-wave with the minimal latency does not always conduct through the fastest motor fiber which determines the onset of M-wave, but may represent a conduction through motor fibers with slower velocity. This disproportionately-prolonged conduction time of the F-wave was never seen during the recovery phase, 12 weeks after the onset of the illness. A conduction block of the fastest motor fiber in the proximal segment is supposed to be a cause of the conduction delay of the F-wave with minimal latency in the acute stage of the Guillain-Barré syndrome.

Acute Disease

[Nerve conduction abnormalities in chronic inflammatory demyelinating polyneuropathy (CIDP)].

Changes in compound muscle action potentials (CMAPs) were evaluated in 13 cases with CIDP by using inching-stimulation technique. The presence of electrophysiological multifocal lesion distinguished CIDP from hereditary demyelinating neuropathy (HDN). The size of each CIDP lesion was sometimes as small as a few millimeters, showing a decrease in CMAP amplitude proximally. No HDN cases revealed such focal changes. It is thus important to demonstrate small lesions with CMAP changes of demyelination-type in diagnosis of CIDP. Decrease in amplitude of proximally-evoked CMAP is essential but sometimes inadequate to determine partial conduction block, because HDN may show decrease in CMAP amplitude, up to 45%, by elbow stimulation as compare to one by wrist stimulation in our series. In determining partial conduction block a standard two-point stimulation can cause an error, because that threshold is quite high over a demyelinated segment, and that a cross stimulation may occur when high voltage stimulation is applied. Multiple-sites stimulation is the most reliable technique to demonstrate convincing changes in CMAPs over small demyelinating lesions. Revival of blocked motor fibers introduces new units to CMAP. In most cases some increase in CMAP amplitude occur first, because remyelinated fibers are slowly-conducting. Some units with shorter latency occasionally revived first, which suggests a possibility of conduction block without morphological background.

Action Potentials

[Evaluation of new system for the detection of IgE antibodies (CAP) in atopic diseases].

An evaluation of a newly developed IgE antibody assay system (CAP) was carried out. There was a clear correlation between IgE antibody titers measured by CAP single and RAST (= 0.642 to 0.979). It turned out that CAP single is more sensitive than RAST and non-specific adsorption of IgE immunoglobulin to the solid phase was assumed to be less in CAP than in RAST. Pathogenic allergens diagnosed either clinically or by in vitro assay systems were compared. The sensitivity and specificity of the CAP system were 94.2% and 87.3%, respectively. CAP multi which binds groups of multiple allergens on the solid phase, was examined for the screening of hypersensitivity to categories of allergens. Statistical sensitivities of CAP multi resided between 63.9% to 86.2%, while the specificities were 98% to 100%, indicating that CAP multi is useful for the exploration of causative allergens. Phadiatop, which fixes multiple inhalant allergens, showed a sensitivity of 89.6%. The specificity of phadiatop was 93.9%, when examined for intrinsic bronchial asthma patients, and 91.2% for normal subjects indicating that phadiatop is more useful than total IgE measurement for the screening of atopic trait.

Adolescent

[Surgical treatment of pulmonary atresia with intact ventricular septum in infancy--analysis of right ventricular growth potential after pulmonary valvotomy].

Our surgical experience involving pulmonary atresia with intact ventricular septum (PPA) between the years 1981 and 1989 is reviewed. Twelve infants aged 3 days to 11 months were studied for right ventricular growth potential with angiocardiography and hemodynamics after transventricular pulmonary valvotomy (TVPV). Ten infants were divided into two groups, 5 infants (Group I) were treated with TVPV only, and the other 5 infants (Group II) required additional surgery after the initial operation (TVPV in 2 cases and TVPV with shunt in 3 cases). Post-operative RV growth potential was evaluated with right ventricular index (RVI) based on the tricuspid valve annulus, right ventricular inlet, and right ventricular outlet dimensions, and with tricuspid annular index (TVI) based on the tricuspid valve annulus normalized by aortic diameter. Follow-up (3-69 months after initial operation) studies demonstrated that the RV cavity increased in Group I (RVI of 15.75 +/- 2.92 preoperatively versus 17.00 +/- 1.57 postoperatively, TVI of 3.04 +/- 0.63 versus 3.85 +/- 0.40). In contrast, the RV cavity in Group II demonstrated a lack of growth (RVI of 9.24 +/- 2.60 versus 9.85 +/- 2.76, TVI of 1.46 +/- 0.46 versus 1.70 +/- 0.80). PPA infants with RVI greater than 11 have been treated successfully with TVPV alone, which may maximize the potential for RV growth, but infants with RVI less than 11 have not experienced RV growth + postoperatively and, therefore, have required second intracardiac operations.

Angiocardiography

[A comparative study of weight of regional lymph nodes in association with the presence of metastasis in primary lung cancer patients].

The weight of regional lymph nodes was measured in 173 patients who underwent surgical resection of the primary lung cancer and lymph nodes from January, 1986 to January, 1989 in our hospital. Histological examination was also performed and correlation of metastasis and the weight of lymph nodes were studied. The average weight of metastatic lymph nodes was 2.34 g while that of non-metastatic ones was 0.83 g indicating a significant (p less than 0.05) increase of weight in metastatic lymph nodes. Although the percentage of metastasis increased as the weight of lymph nodes increased, 7.6% of lymph nodes weighing less than 0.5 g was positive for metastasis. On the other hand, 66.7% of the lymph nodes weighing more than 3.0 g in adenocarcinoma and 34.5% in squamous cell carcinoma were positive for metastasis indicating the difference of the metastatic tendency to the lymph nodes between the two histological types. The comparative study of the weight of each lymph node station according to the JJC criteria demonstrated the difference of average weight of non-metastatic lymph nodes among each lymph node station. The average weight of pretracheal (#3), subcarinal (#7), interlobar (#11), and segmental (#12) lymph nodes without tumor metastasis were more than 1.0 g, however those of anterior mediastinal (#3a), paraesophageal (#8), and pulmonary ligament (#9) were less than 0.5 g. The average weight of metastatic lymph nodes in each lymph node station was in proportion to those of non-metastatic ones.

Adenocarcinoma

[Results of noncurative resection of primary lung cancer (II): Comparative study of the former (1952-1978) and latter (1979-1988) period].

Results of surgical treatment for primary lung cancer patients who underwent noncurative resection from 1979 to 1988 (the latter period) in our department were compared with those treated before 1979 (the former period). Noncurative rate decreased from 39.8% (the former period) to 28.0% (the latter period). The common causes of noncurative resection in the former period was tumor rest in mediastinal lymph nodes (34.0%) and that in chest wall or diaphragma (Ch + Dia; 31.6%) while those of the latter period were intrapulmonary metastasis (p.m.: 21.4%) and tumor rest in the mediastinal lymph nodes. Five year survival rate improved significantly from 5.6% of the former period to 28.6% of the latter period (p less than 0.01, Generalized Wilcoxon test). Compared with the 5 year survival rate of the former groups with pleuritis carcinomatosa, pleural dissemination, p.m. and Ch + Dia, the rate of the latter groups showed significant improvement from 0%, 0%, and 6.25% to 53.3%, 38.6% and 22.1%, respectively.

Bronchi

[Quality of life of patients after esophagectomy for esophageal cancer].

Quality of life of 79 patients who underwent esophagectomy for esophageal cancer and survived more than one year was evaluated by a questionnaire method. About 90% of patients had a good appetite, taking ordinary solid foods, and 69% were satisfied with the daily amount of foods. About 40% of patients complained of passage disturbance on swallowing, abdominal pain or diarrhea after meal. Fifty seven per cent of patients had frequent episodes of cough and sputum, and 20% were not able to go up the stairs to the third floor because of short breath. Thirty two per cent of patients with recurrent nerve paresis and even 5% without paresis had a trouble in daily conversation. These physical distresses were thought to be useful indicators for the doctor to evaluate the quality of life of patients. Additionally, about 30% of patients had a tendency of mental depression postoperatively. Fifty six per cent of patients who had worked before operation returned to work or were doing a lighter work than before. The psychological factor and social rehabilitation were suggested to be very important, when evaluated from the patient's side. Especially in case of aggressive surgery for esophageal cancer, postoperative quality of life of patients should be carefully considered from the viewpoints of both the patient and doctor.

Aged

[A double blind study of the effectiveness of ketotifen in preventing the development of asthma in atopic dermatitis patients].

Many asthmatic children have experienced atopic dermatitis in their younger days. As it is very difficult to cure childhood asthma we attempted to determine the anti-allergic drug effects in preventing the development of asthma by using ketotifen on atopic dermatitis patients. The study was designed as a placebo controlled double blind trial of 128 atopic dermatitis patients aged from 2-34 months. 91 patients were given complete analysis in the study, 33 patients were given only a safety rate and 4 patients were dropped. The 91 patients were followed for 52 weeks. Our primary finding was that the development of bronchial asthma was inhibited in the ketotifen group compared to the placebo controlled group with a statistically significant degree (p less than 0.001). We also found that clinical symptoms of atopic dermatitis were significantly improved in the ketotifen group (p less than 0.001). Only 5 patients complained of mild side effects.

Age Factors

In vivo invasion assay of low passage cultured cells derived from human lung cancer using deepithelialized rat tracheas xenotransplanted into nude mice.

Human lung tumor-derived cell lines with low passage generation were transplanted into nude mice to determine their growth behavior and invasive potential. Six cell lines (HKT-2, HKT-3, HKT-5, HKT-6, HKT-7, HKT-8) were inoculated into deepithelialized rat trachea (5 x 10(5) cells/trachea). After cell inoculation, the tracheas were sealed and transplanted into the subcutis of nude mice. In a parallel experiment, these cell lines (1 x 10(6) cells) were injected s.c. In the subcutis, the tumor take rate of HKT-3, the lowest of all, was only 13% with a long latency period of 18 weeks, and 3 cell lines (HKT-2, HKT-3, HKT-7) did not show any invasive growth to the surrounding tissue. In rat tracheas, all cell lines proliferated within 3 weeks, and 4 of them (HKT-2, HKT-5, HKT-6, HKT-8) showed invasive growth to the tracheal wall within 1-2 weeks. Cells growing in the tracheal wall showed higher [3H]thymidine labeling indexes and greater atypia, such as larger nuclei and prominent nucleoli, than those in the tracheal lumen. The s.c. tumor take rate correlated with the incidence of invasive growth to the tracheal wall. The survival of the patients originally bearing the six tumors also correlated closely with the invasive potential of this system. These results indicate that the system using low passage cell lines can evaluate the invasive potential shortly after the inoculation of a relatively small number of cells and can be used as a clinically reliable biological invasion assay.

Adenocarcinoma

Effect of tetragastrin on azaserine-induced carcinogenesis in rat pancreas.

The effect of tetragastrin on pancreatic tumors induced by azaserine was investigated in Wistar rats. Rats were given 25 weekly injections of 10 mg/kg body weight of azaserine and 1 mg/kg body weight of tetragastrin as a suspension in olive oil every other day. Carcinogen-induced pancreatic lesions were examined by histochemical techniques, and were classified as ATPase-positive or ATPase-negative. In week 62, quantitative histological analysis showed that prolonged administration of tetragastrin had little or no influence on the number and size of the carcinogen-induced pancreatic lesions, although it caused significantly increased cell proliferation, indicated by a greater labelling index of the pancreatic acinar cells.

Adenosine Triphosphatases

Attenuating effect of bromocriptine on cysteamine anticarcinogenesis of stomach cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine.

The effect of bromocriptine on inhibition by cysteamine of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine was investigated in inbred Wistar rats. After 25 weeks of p.o. treatment with N-methyl-N'-nitro-N-nitrosoguanidine, rats were given injections every other day: cysteamine (50 mg/kg body weight); cysteamine (50 mg/kg body weight) plus bromocriptine (0.5 or 0.25 mg/kg body weight); or bromocriptine (0.5 or 0.25 mg/kg body weight). In week 52, the group treated with cysteamine showed a significantly decreased incidence of gastric cancers. Concomitant treatment with bromocriptine at 0.5 but not at 0.25 mg/kg body weight significantly attenuated the inhibitory effect of cysteamine on gastric carcinogenesis. Administration of bromocriptine alone at either dosage had no influence on gastric carcinogenesis. The labeling index of the antral mucosa was significantly reduced in rats treated with cysteamine and significantly higher in those treated concomitantly with bromocriptine at 0.5 mg/kg body weight than in those treated with cysteamine alone. These findings indicate that cysteamine suppressed gastric carcinogenesis and that bromocriptine at high dosage attenuated this inhibition. These findings also suggest that dopamine is involved in the mechanism of inhibition of gastric carcinogenesis by cysteamine.

Animals

Inhibition by gamma-amino-n-butyric acid and baclofen of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effect of gamma-amino-n-butyric acid (GABA), the GABA(A) receptor agonist muscimol (5-aminomethyl-3-hydroxyisoxazole), and the GABA(B) receptor agonist baclofen [4-amino-3-(4-chlorophenyl)butanoic acid] on the incidence and number of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine was investigated in Wistar rats. Rats received alternate-day i.p. injections of 500 or 1000 mg/kg of body weight GABA, 0.25 or 0.5 mg/kg of body weight muscimol, or 4 or 8 mg/kg of body weight baclofen after 25 wk of p.o. treatment with the carcinogen. Prolonged administration of GABA at 1000 mg/kg of body weight, but not at 500 mg/kg of body weight, and of baclofen at 4 and 8 mg/kg of body weight significantly decreased the incidence and number of gastric cancers of the glandular stomach in Wk 52, but long-term muscimol administration had no influence. Histologically, GABA at the high dosage and baclofen at both dosages significantly decreased the labeling index of the antral mucosa and significantly increased the serum gastrin level. Furthermore, baclofen at both dosages significantly decreased antral pH and significantly increased gastric acid secretion. These findings indicate that GABA inhibits gastric carcinogenesis via the GABAB receptor and that this effect may be related to its effect in decreasing the proliferation of antral mucosa.

Animals