Simultaneous localization of histamine and factor VIII-related antigen in the endothelium of the human umbilical vein

Simultaneous immunoelectron microscopic localization of histamine and factor VII-related antigen was examined on the same ultrathin section of the endothelium of the human umbilical vein from full-term deliveries by means of the double-immunolabeling technique. Small gold particles demonstrating antibody reaction with histamine are preferentially located in the cytoplasmic matrix and organelles, especially in mitochondria and on the luminal membrane surface of the endothelial cells. The gold particles representing histamine immunoreactivity also located on some of Weibel Palade (WP) bodies. In contrast, large gold particles demonstrating factor VII-related antigen are concentrated preferentially on most WP bodies. Single labeling of either histamine or factor VIII-related antigen shows similar results to those of the double labeling. The present study indicates that some WP bodies are involved in storage of both factor VIII-related antigen and histamine, but others store factor VIII-related antigen only. This difference in contents of WP bodies may be induced during the development and maturation process of this inclusion. At any rate, it is reasonable to consider that WP bodies have important roles in both vascular tonus and hemostasis during the vascular obliteration.     

Disturbed pyloric motility in Ws/Ws mutant rats due to deficiency of c-kit expressing interstitial cells of Cajal

Interstitial cells of Cajal (ICC) are believed to lnitlate the basic contractile activity of the gastrointestlnal tract. Interstitial cells of Cajal express c-kit receptor tyroslne kinase and are deficient in Ws/Ws mutant rats with a small deletion of the c-kit gene . As Ws/Ws rats show remarkable bile reflux to the stomach, the contraction pressure of the pylorus was compared between Ws/Ws and control +/+ rats. The contraction pressure of the pylorus was measured using a mlcrotransducer, which was Inserted through a pln-hole in the anterlor wall of the stomach under anesthesla. The magnitude of bile reflux was estimated by measurlng the content of bile acids In the stomach. The c-kit messenger RNA-expressing cells were detected by in sltu hybrldlzatlon. Frequency and the maxlmum pressure of the contractlon were comparable between Ws/Ws and +/+ rats, but the duration of the contractlon was significantly shorter In Ws/Ws rats than In +/+ rats. The number of c-kit messenger RNA-expresslng ICC in the pylorus of Ws/Ws rats was 1.7% that of +/+ rats. The bile reflux observed in Ws/Ws rats was attributed to the decrease in the duration of the pyloric contraction, which appeared to result from the deficlency of c-kit messenger RNA-expressing ICC.     

Antifungal activities of tacrolimus and azole agents against the eleven currently accepted Malassezia species

The lipophilic yeast Malassezia is an exacerbating factor in atopic dermatitis (AD) and colonizes the skin surface of patients with AD. With the goal of reducing the number of Malassezia cells, we investigated the antifungal activities of a therapeutic agent for AD, tacrolimus, and the azole agents itraconazole and ketoconazole against Malassezia species in vitro. We examined 125 strains of the 11 currently accepted Malassezia species by using the agar dilution method. All strains of the 11 Malassezia species were very susceptible to both azole agents, with MICs ranging from 0.016 to 0.25 mug/ml. Tacrolimus had antifungal activities against half of the strains, with MICs ranging from 16 to 32 mug/ml. Two of the major cutaneous floras, Malassezia globosa and Malassezia restricta, have several genotypes in the intergenic spacer region of the rRNA gene; the azole agents had slightly higher MICs for specific genotype strains of both microorganisms. A combination of azole agents and tacrolimus had a synergistic effect against Malassezia isolates, based on a fractional inhibitory index of 0.245 to 0.378. Our results provide the basis for testing these agents in future clinical trials to reduce the number of Malassezia cells colonizing the skin surface in patients with AD.     

Granuloma associated with Trichosporon asahii infection in the lung: Unusual pathological findings and PCR detection of Trichosporon DNA.

We describe the first case of a Trichosporon asahii infection of the lung characterized by an epithelioid granuloma with multinucleated giant cells. The patient died of respiratory failure due to lung fibrosis and lung cancer. Autopsy showed primary lung cancer with metastasis, lung fibrosis, and a focal infectious lesion containing the filamentous and yeast forms of a fungus. From its shape the fungus was judged to be Trichosporon, but unusual pathological findings revealed an epithelioid granuloma with multinucleated giant cells surrounding the hyphae and yeast cells. Immunohistochemical staining was performed using the specific Trichosporon spp. monoclonal antibodies and DNA identificationn was done by the PCR. The results showed this case to be a localized Trichosporon asahii infection. Hypersensitivity pneumonitis (HP) due to Trichosporon spp. with its pathological finding of inflammation with granuloma is common, but infections with granulomatous inflammation are extremely rare. This case suggests that Trichosporon infection may develop into granuloma with multinucleated giant cells.     

Fastigiofugal fibers encoding horizontal and vertical components of saccades as determined by microstimulation in monkeys.

To identify the routes by which oculomotor vermis signals control eye movements (saccadic signals), saccades evoked by microstimulation were studied in the region of the uncinate fasciculus (UF) and juxtarestiform body (JB) in the macaque monkey. Anatomical pathways of axons from the fastigial oculomotor region (FOR) were studied by anterograde transport of wheatgerm agglutinin conjugated horseradish peroxidase (WGA-HRP). The routes were identified by comparing maps of low threshold for evoking saccades with the anatomical map of anterogradely labeled axons arising from the FOR. Microstimulation of a region of the UF and JB demonstrated that saccadic signals are carried exclusively by decussated FOR axons which leave the cerebellum via the contralateral UF. The fibers in the JB do not carry saccadic signals. The horizontal component of saccadic signals is conveyed by fibers in the descending limb of the UF, while the vertical component is conveyed by a smaller group of fibers which separate from the UF and enter the midbrain with the contralateral superior cerebellar peduncle.     

Fundamental and clinical studies of ceftizoxime suppositories in pediatrics

Fundamental and clinical studies were carried out on ceftizoxime suppository (CZX-S), and the following results were obtained in pediatrics. In 4 patients of the CZX-S 125 mg-administered group (9.4-9.9 mg/kg), the serum concentration of CZX reached a peak of 5.55 micrograms/ml on the average, 30 minutes after dosing, i.e. at the time of initial blood collection, and decreased gradually to 0.20 microgram/ml 6 hours after dosing. The half-life was 1.09 hours. In 5 patients of the CZX-S 250 mg-administered group (8.4-18.1 mg/kg), the serum concentration of CZX peaked at 7.07 micrograms/ml on the average and then gradually declined to 0.16 microgram/ml 6 hours after dosing. The half-life was 1.00 hour. The urinary recovery rate varied as widely as 6.5-38.0% in all the patients of both groups. CZX-S was given to total 19 patients; 8 patients with urinary tract infection (UTI), 3 with pharyngitis or tonsillitis, 4 with bronchitis, 2 with pneumonia, 1 with otitis media and 1 with staphylococcal scalding skin syndrome. The overall effect of CZX-S in 15 patients was "effective" or better response, with an effectiveness rate of 83.3%, except one who discontinued the drug because of side effects. CZX-S was given to most of the patients weighing 15 kg or higher in a dose of 250 mg 3-4 times a day and frequently to patients weighing less than 15 kg in a dose of 125 mg 3-4 times a day. As to side effects, slight diarrhea was encountered in 1 patient. Laboratory examinations disclosed an increase in GOT in 1 patient, which returned to normal after continual insertion of the suppository.     

Sylvian fissure arteriovenous malformations

We have operated on 16 cases of arteriovenous malformation (AVM) in and around the sylvian fissure. We call these lesions "sylvian fissure AVMs" and classify them into four subdivisions, namely, pure, lateral, medial, and deep AVMs. By others, they have been variously called AVMs of the basal ganglia, insula, anterior choroidal artery, frontal lobe, or temporal lobe. These sylvian fissure AVMs showed similar angiographic findings: the feeders in all cases were branches of the middle cerebral artery; in some cases, additional feeders from the anterior and posterior choroidal and posterior communicating arteries were present also. We describe the characteristic features of these AVMs from the anatomical and surgical points of view. The surgical results were satisfactory in 15 cases (no additional neurological deficits), and 1 patient died.     

A comparative, well-controlled study of ceftizoxime suppository against ceftizoxime intravenous injection in infantile acute pneumonia

We have attempted to clinically define the therapeutic usefulness of ceftizoxime suppository (CZX-S) in children with bacterial pneumonia, in a randomized trial. Intravenous injection of ceftizoxime (CZX) was used as the control. The results are summarized below. Subjects were inpatients with bacterial pneumonia, ranging in age from 9 months to 7 years and 10 months. As a rule, the daily dose was either four 250 mg (in potency) suppositories given at 6-hour intervals or 60 mg/kg body weight intravenous CZX (control) given in 4 injections at 6-hour intervals over a period of 7 days. The number of children in the study was 67. These children were divided into 2 dosage groups (suppository, 35; injection, 32) with matching pretreatment background factors. The severity of the target disease in the majority of the children was "moderate". The rate of therapeutic effectiveness was 97.1% for the suppository and 93.8% for the injection, and did not differ significantly between the 2 groups. Rates of efficacy by severity, presence or absence of underlying diseases, daily dose and/or complications were high without exception, and did not differ significantly between the 2 groups. Eradication rates for causative microorganisms, as studied in 16 children of each group, were both 93.8%. The 2 most frequently isolated causative organisms were Haemophilus influenzae and Streptococcus pneumoniae. Side effects were examined for 36 children of each group. The frequency of side effects did not differ significantly between the suppository group (2 with diarrhea and 1 with abdominal pain) and the injection group (1 with urticaria), and 8.3% and 2.8%, respectively. The frequency of abnormal laboratory test findings differed significantly (P less than 0.01) with respect to eosinophilia which occurred in 7 (20.6%) of the injected subjects but was not encountered in the subjects treated with suppositories. Other abnormal laboratory findings included thrombocytosis in 3 (14.3%) of the injection group and increased GOT in 1 (3.2%) of the suppository group. The suppository formulation of CZX appears to be a highly useful substitute for the injectable form, and should find a special use in children whose treatment with injections experiences some difficulty.     

Potential predictors of the onset of focal intestinal perforation in extremely low birth weight infants based on an analysis of coagulation and fibrinolysis markers at birth: A case-control study based on ten years of experience at a single institution

Purpose: We aimed to investigate potential predictors of focal intestinal perforation (FIP) in extremely low birth weight infants (ELBWIs) among coagulation and fibrinolysis markers at birth.Methods: We reviewed the medical records of FIP patients and their coagulation and fibrinolysis markers at birth between 2010 and 2019, and matched patients according to gestational age. FIP was diagnosed based on macroscopic intestinal perforation with a punched-out lesion without necrosis. Patient characteristics and blood test results, including coagulation and fibrinolysis marker levels, were compared between the groups.Results: Two hundred forty ELBWIs were enrolled in this study (FIP, n = 18; controls, n = 222). In the FIP group, the gestational age at birth was significantly younger (p = 0.023) and the birth weight was significantly lower (p = 0.007) in comparison to the control group. Furthermore, the FIP group showed significantly lower levels of fibrinogen (p = 0.027) and factor XIII (F-XIII) (p = 0.007). The receiver operating characteristics curves for fibrinogen and F-XIII revealed that the 95% confidence intervals of fibrinogen and F-XIII were 0.530–0.783 (p = 0.027), and 0.574–0.822 (p = 0.007), respectively.Conclusions: This is the first report focusing on coagulation and fibrinolysis markers in FIP patients at birth. The fibrinogen and F-XIII values at birth are potential predictors of FIP in ELBWIs.Type of Study: Study of Diagnostic Test (Case Control Study)Level of Evidence: Level IV     

A multi-institutional survey of the quality of life after treatment for uterine cervical cancer: a comparison between radical radiotherapy and surgery in Japan

This study aimed to research the post-treatment quality of life (QOL) between radiotherapy (RT)- and operation (OP)-treated early cervical cancer survivors, using separate questionnaires for physicians and patients. We administered an observational questionnaire to patients aged 20–70 years old with Stages IB1–IIB cervical cancer who had undergone RT or OP and without recurrence as outpatients for ≥6 months after treatment. We divided 100 registered patients equally into two treatment groups (n = 50 each). The average age was 53 and 44 years in the RT and OP groups, respectively. The RT group included 34 and 66% Stage I and II patients, respectively, whereas the OP group included 66 and 34% Stage I and II patients, respectively. The OP group included 58% of patients with postoperative RT. Combination chemotherapy was performed in 84 and 48% of patients in the RT and OP groups, respectively. On the physicians’ questionnaire, we observed significant differences in bone marrow suppression (RT) and leg edema (OP). On the patients’ questionnaire, significantly more patients had dysuria and leg edema in the OP group than in the RT group, and severe (Score 4–5) leg edema was significantly higher in the post-operative RT group than in the OP only group. The frequency of sexual intercourse decreased after treatment in both groups. On the patients’ questionnaire, there were no significant differences between the two groups regarding sexual activity. These findings are useful to patients and physicians for shared decision-making in treatment choices. The guidance of everyday life and health information including sexual life after treatment is important.