Biomedical subjects
Publications and source records attributed to T Tezuka.
A 26-year-old man had a primary infection or reinfection of genital herpes due to herpes simplex virus (HSV) type 2 complicated with herpetic urethritis. By analysis of the restriction endonuclease digestion pattern of the viral DNA, two isolates, one from the penile lesion and one from the urethra, were identified as the same strain.
In old age, the epidermis tends to become dry and flaky, especially on the lower legs. However, this does not occur on the face, although long-term ultraviolet light irradiation has important effects on the differentiation of facial keratinocytes. Therefore, the differentiation of the epidermal cells of the facial skin in the young and the aged was immunohistochemically examined using antibodies against four differentiation products: filaggrin, involucrin, cystatin A (CTA) and carbonic anhydrase-like protein. The results showed that there was no difference in the amounts of the above three proteins in facial skin between the young and the aged with the exception of CTA. The amount of CTA was much greater in the facial skin of the aged. However, there was a striking decrease of filaggrin content in the skin of the lower leg in the aged. One of the reasons why no scaly skin is found on the face in the aged may be the fact that especially filaggrin does not decrease with aging.
Detection of varicella-zoster virus (VZV) DNA was carried out in the conjunctivas of 18 patients with herpes zoster by polymerase chain reaction. The rate of VZV DNA detection in conjunctivas was 3/4 in herpes zoster ophthalmicus associated with eruption on the dorsum nasi, 2/5 in herpes zoster ophthalmicus without eruption on the dorsum nasi, 1/2 in herpes zoster with eruption on the cheek and lower jaw, 1/2 in generalized herpes zoster and 0/5 in herpes zoster associated with eruption on the trunk or extremities, respectively. The reason for the detection of VZV DNA in conjunctivas is discussed.
A 26-year-old woman with erythema infectiosum is reported. She had small faint erythemas on her extremities and congestion of palpebral and bulbar conjunctiva of both eyes. Human parvovirus B19 (B19) DNA was detected in the specimen of the conjunctiva by the polymerase chain reaction. This result suggests that conjunctivitis in erythema infectiosum may cause the B19 infection.
We report a case of lymphocutaneous nocardiosis due to Nocardia brasiliensis, marked by multiple subcutaneous nodules and abscesses on the extensor aspect of the left forearm in a 53-year-old woman with systemic lupus erythematosus. Nine months before she was first examined, she had fallen on a concrete surface. A nodule had appeared 2 months later at the same site and had expanded and been followed by others, which finally covered most of the extensor aspect of the forearm. We speculated that the bacteria may have been conveyed retrogradely via the lymph vessels in a distal direction, perhaps as a result of the trauma and the subsequent development of an intradermal lesion.
Pharmacokinetic and clinical studies on biapenem (L-627), a newly developed carbapenem, were performed and the following results were obtained. 1. Absorption/excretion: Pharmacokinetics of biapenem was studied in 14 children at doses of 6 mg/kg and 12 mg/kg administered through 30 minutes-drip infusion. Peak plasma levels and plasma half-lives of the 2 doses were 22.5, 29.9 micrograms/ml, and 0.84, 0.85 hours, respectively. Their urinary recovery rates were 54.5 to 76.1% and 37.3 to 59.5%, respectively. Cerebrospinal fluid levels of biapenem in two patients with purulent meningitis were 0.88 and 2.72 micrograms/ml, and the penetration rates were 3.7 to 8.3%. 2. Clinical study: Forty-nine patients were treated with biapenem at doses exceeding 90 to 100 mg/kg/day for purulent meningitis and at doses between 15.0 and 36.0 mg/kg/day for other infections. Biapenem gave "Excellent" or "Good" responses in 48 cases, hence an efficacy rate of 98.0% was obtained. Only one patient with pneumonia showed a fair response. No adverse reactions were observed. Abnormal laboratory test results were noted in 7 patients including elevation of GOT, GPT, and eosinophils. In no cases the treatment had to be discontinued.
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In order to develop a novel monoclonal antibody reacting with the cell membrane protein which could be a receptor for cell growth, differentiation or an adhesion molecule, keratinocytes from psoriatic epidermis and A-431 cell line were used to immunize BALB/c mice. A monoclonal antibody, KA-1 was developed. KA-1 reacts with the cell membranes of the whole epidermis with the exception of the stratum corneum cells and the basal cell membrane in contact with the basement membrane. In electron microscopy, the antigenic site was located on the surface of the microvilli of the cultured keratinocytes, especially at the contact area with another villi, the cell membrane or collagen. The antigenic protein was a 44-kDa protein which was different from E-cadherin in both molecular weight and cross-reactivity.
As the Ted-R-1 monoclonal antibody yields fluorescence on the keratohyalin granules, in the cytoplasm of the lower stratum corneum cells and on the cell membrane region of the stratum corneum in indirect immunofluorescent examination, the location of the antigen of this Ted-R-1 monoclonal antibody was examined by the post-embedding, immunoelectron microscopic technique using gold labelled antibody. The number of gold particles located on the keratohyalin granules was 184.00 +/- 28.69 per micron2. In contrast, there were only a few gold particles in the nucleus and the cytoplasm of the stratum granulosum (3.85 +/- 1.34) and none were found in the intercellular spaces of these cells (< 1.00). On the other hand, they were diffusely located in the lower two to three cell layers of the stratum corneum (319.75 +/- 44.41) and on the inner surface of the marginal band of the upper cell layers of the stratum corneum, but only a few were located in the cytoplasm of the upper stratum corneum cells (12 +/- 7.00). These observations indicate that the Ted-R-1 antigen locates on both keratohyalin granules and the inner surface of the marginal band of the upper part of the stratum corneum cell layers.
We report a girl with Ph1-positive ALL with the aberrant BCR-ABL product. In this case, bcr exon 3 jointed not to ordinal abl exon 2 but to exon 3 resulting in the production of a 203 kD BCR-ABL fusion protein with marked tyrosine kinase activity. To our knowledge, this is the first report of an aberrant BCR-ABL product in childhood. This case was characterized with younger age and low leucocyte count at the onset, but relapsed early like the typical Ph1-positive ALL, suggesting the diversity in the clinicopathogenesis of Ph1-positive ALL.
In order to facilitate the isolation of C. pneumoniae, strain similar TWAR, with high frequency, we investigated the effect of various factors on the infectivity of Chlamydia using two laboratory strains, C. pneumoniae TWAR and C. trachomatis serovar D. The factors tested were the effects of different temperatures for storage conditions, saliva from healthy person, storage media for Chlamydia, and the frequency of freezing and thawing. Chlamydial suspension was prepared in the two media, SPG (sucrose-phosphate-glutamate buffer pH 7.5), and CT-GM (culture medium for Chlamydia which contains 1 micrograms/ml cycloheximide and 0.04% glucose). Chlamydial suspension was allowed to stand in each of four different thermal conditions: 37 degrees C, room temperature (25 degrees C), 4 degrees C, 0 degrees C and -75 degrees C for 1, 3, 6, 24, 48, 72, 96, 120 and 144 hours. For storage at -75 degrees C, one of three groups of glass vial tubes containing Chlamydia was covered with an "airmat" to prevent the rapid freezing of Chlamydia. The effect of various factors on the infectivity was assayed by inoculation of the suspension on HeLa 229 cell monolayers. Results showed that the infectivity rapidly decreased at 37 degrees C and room temperature, while at 4 degrees C, 0 degrees C and -75 degrees C, relatively high infectivity was maintained and contained until days 4 to 6. This decreasing pattern was similar to among the media used. We were not able to find any differences in the infectivity among the samples with or without the "airmat".(ABSTRACT TRUNCATED AT 250 WORDS)
We described a forty-four-year-old female who was scratched by her cat, and developed lymphadenopathy. Cat scratch disease skin-test was positive. Cat scratch disease is well known, but there are not many reports in Japan. Reports of cat scratch disease will increase as the pathogen was recently detected. Attention must be drawn to zoonosis containing cat scratch disease.
Pharmacokinetic and clinical studies on S-1108, a new oral cephem antibiotic, were performed in the field pediatrics. The following results were obtained. 1) Antibacterial activities Antibacterial activities of S-1006, the active form of S-1108, were studied against clinically isolated strains of (Staphylococcus aureus (n = 5), Streptococcus pneumoniae (n = 6), Streptococcus pyogenes (n = 3), Haemophilus influenzae (n = 8), Branhamella catarrhalis (n = 5) and Haemophilus parainfluenzae (n = 2). MIC values ranged < or = 0.025-1.56 for GPC and < or = 0.025-0.78 microgram/ml for GNR. 2) Absorption and excretion Blood concentrations and urinary excretion rates of S-1108 were measured upon administration of S-1108 after meal at dose of 3 mg/kg (n = 4), 4 mg/kg (n = 1) and 6 mg/kg (n = 1). The peak blood concentrations of S-1006 at a dose of 3 mg/kg (n = 4), ranged from 0.57 to 1.82 micrograms/ml at 1, 2 and 4 hours after dosing. Mean pharmacokinetic parameters T1/2 and AUC were 1.29 +/- 0.69 hours and 4.47 +/- 2.25 micrograms.hr/ml, respectively. At a dose of 4 mg/kg and 6 mg/kg, peak concentrations were 1.79 and 1.27 micrograms/ml at 2 and 3 hours after treatment. T1/2 and AUC were 1.34 and 1.11 hours, and 8.19 and 5.65 micrograms.hr/ml, respectively. Urinary recovery rates ranged from 13.0 to 37.2% for the first 8 hours after administration. 3) Clinical studies Clinical efficacies were examined in 32 cases of various pediatric infections including 5 cases of acute pneumonia, 11 cases of bronchitis, 2 cases of scarlet fever, 8 cases of tonsillitis, 1 case of pharyngitis, 2 cases of otitis media and 3 cases of UTI. Clinical efficacy rate was 96.9% (31/32) and bacteriological eradication rate was 87.1% (27/31). There were no side effects and abnormal laboratory test values except 1 case (Eosino. 2-->10%) in the 32 cases.
Bacteriological, pharmacokinetic and clinical studies on cefditoren pivoxil (CDTR-PI, ME 1207) in granules, a new oral cephalosporin, were performed in the field of pediatrics. The results are summarized below. 1. Antibacterial activities: Antibacterial activities of CDTR were studied against Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Haemophilus parainfluenzae and Branhamella catarrhalis in comparison with those of cefteram (CFTM), cefixime (CFIX), cefaclor (CCL), cefpodoxime (CPDX) and cefotiam (CTM). MIC80's of CDTR against S. aureus, S. pneumoniae, S. pyogenes, H. influenzae, H. parainfluenzae and B. catarrhalis were 1.56, 0.39, < or = 0.025, < or = 0.025, 0.05 and 0.20 micrograms/ml, respectively. These results showed that CDTR has high antibacterial activities against these organisms. 2. Absorption and excretion: Serum concentrations and urinary recovery rates of CDTR-PI (administered in granules) were determined. Upon single oral doses of 3 mg/kg and 6 mg/kg, the peak serum concentrations were 0.5-2.45 micrograms/ml at 2 to 4 hours and 1.79-4.05 micrograms/ml at 1 to 4 hours, respectively, and T 1/2 was 1.07-9.67 hours and 0.99-3.00 hours, respectively. At 8 hours after dosing, serum concentrations were 0-0.87 micrograms/ml with a dose of 3 mg/kg and 0.27-0.73 micrograms/ml with 6 mg/kg. These values indicated that the drug has a dose-dependent pharmacokinetic behavior. Urinary recovery rates in the first 8 hours were 12.9-34.2% with a dose of 3 mg/kg and 11.8-26.9% with 6 mg/kg. 3. Clinical study: Clinical efficacies were examined in a total of 81 cases consisting of 20 cases of acute bronchitis, 13 of acute pneumonia, 21 of tonsillitis, 5 of pharyngitis, 7 of scarlet fever, 2 each of impetigo, otitis media and purulent cervical lymphadenitis, 1 of pertussis and 8 of UTI. The clinical efficacy rate was 97.5% (79/81), and bacteriological eradication rate was 100% (76/76). As for side effects, 2 cases of watery stools and 1 case of minor elevation of GPT were observed.
The postoperative arrhythmias (exclusive of sinus tachycardia) was reviewed in 77 patients (male: 69, female: 8, mean age: 63.9 years) who underwent esophagectomy for esophageal carcinoma. The results were as follows: 1. The incidence of postoperative arrhythmias in all patients but seven who had preoperative chronic atrial fibrillation (af) or pacemaker rhythm was 47.1%, and af was observed most frequently (45.5%). Postoperative arrhythmias occurred in patients with abnormal preoperative electrocardiographic findings more often than in those with normal preoperative electrocardiographic findings (53% vs 41%). The incidence of postoperative arrhythmias in aged patients (> or = 66 years old) was significantly higher than that in younger patients (< or = 65 years old) (64% vs 35%, p < 0.05). Other risk factors for postoperative arrhythmias were sex and history of hypertension. 2. Postoperative arrhythmias occurred more often in patients who underwent blunt dissection of the thoracic esophagus and reconstruction using the whole stomach via the posterior mediastinal route than in those who underwent esophagectomy with right thoracotomy and reconstruction using the gastric tube via the poststernal route (60.0% vs 45.0%). 3. Most supraventricular premature contractions and ventricular premature contractions occurred immediately after surgery or on the first postoperative day, and af often occurred during the first postoperative night or the second postoperative day. 4. For treatment, various antiarrhythmic agents were administered according to the patient's condition. Glucose-insulin-kalium therapy was especially effective (63%). None of the arrhythmias was fatal.
Both keratohyalin granules (KHG) and cornified envelopes were stained histochemically in an indirect immunofluorescent study by antiphosphorylated cystatin alpha antibody, indicating that phosphorylated cystatin alpha is a component of the cornified envelope proteins. When phosphorylated cystatin alpha (P-cystatin alpha) was incubated with epidermal transglutaminase (TGase) and Ca2+ ions, polymerized protein was produced by formation of epsilon-(gamma-glutamyl)lysine cross-linking peptide bonds between lysine residues of cystatin alpha and glutamine residues of suitable protein(s) in the enzyme preparation. However, phosphorylated and non-phosphorylated cystatins were polymerized to similar extents by the TGase. Immunofluorescent and immunoelectron microscopic observations revealed that P-cystatin alpha could be detected in vivo in the KHG and cornified envelopes. Treatment of sphingosine, a specific inhibitor of protein kinase C, markedly suppressed the incorporation of cystatin alpha into KHG. Thus phosphorylation of cystatin alpha by protein kinase C may play an important role in targeting cystatin alpha into KHG.
A 27-year-old woman developed chickenpox postpartum. Her 2-month-old son who was breast fed also acquired chickenpox 16 days after the onset of the mother's illness. Varicella-zoster virus (VZV) DNA was detected in maternal breast milk by the polymerase chain reaction. These results suggest that transmission of VZV may occur via maternal breast milk.
We studied eight children (seven girls and one boy, of whom three are siblings) with accelerated growth, premature pubarche and/or hirsutism between the ages of 7 and 9.5 years. These patients were studied for the presence of adrenal steroidogenic defect by adrenocortico tropic hormone (ACTH) stimulation testing (Cortrosyn, 0.25 mg iv bolus dose). Baseline and stimulated 17-hydroxypregnenolone (delta 5-17P), 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA), androstenedione (delta 4-A), testosterone, and cortisol levels were measured. Six children, including three siblings, were diagnosed with a mild form of 3 beta-hydroxysteroid dehydrogenase deficiency based upon the elevated response of serum delta 5-17P and the elevated ratio of delta 5-17P/17-OHP and of DHEA/delta 4-A to ACTH stimulation. Thus, a mild form of 3 beta-hydroxysteroid dehydrogenase deficiency may not be uncommon in children with accelerated growth, premature pubarche and/or hirsutism and routine assay of delta 5-steroid metabolites should be generally available.