Preparation of ceramic microspheres for in situ radiotherapy of deep-seated cancer

Radiotherapy is one of the most effective treatments for cancers. However, external irradiation provides only small doses to deep-seated cancers, and often causes damage to healthy tissues. It has been reported that 20-30 microm diameter 17Y(2)O(3)-19Al(2)O(3)-64SiO(2) (mol%) glass microspheres are useful for the in situ irradiation of cancers. Yttrium-89 (89Y) in this glass can be neutron bombarded to form the beta-emitter 90Y (half-life=64.1h). When injected in the vicinity of the cancer, such activated glass microspheres can provide a large localized dose of beta-radiation. The Y(2)O(3) content of the glass in the microspheres is limited to only 17 mol%. Chemically durable microspheres with a higher Y(2)O(3) content need to be developed. Phosphorus-31 (31P) with 100% natural abundance can also be activated by neutron bombardment to form the beta-emitter 32P (half-life=14.3d). Chemically durable microspheres containing a high phosphorus content are expected to be more effective for cancer treatment. We prepared pure Y(2)O(3) and YPO(4) microspheres using a high-frequency induction thermal plasma melting technique, and investigated the resulting structure and chemical durability. We successfully prepared smooth, highly spherical polycrystalline Y(2)O(3) and YPO(4) microspheres with diameters in the range 20-30 microm. Both the Y(2)O(3) and YPO(4) microspheres showed high chemical durability in saline solutions buffered at pH=6 and 7. These microspheres are expected to be more effective than the conventional glass microspheres for the in situ radiotherapy of cancer.     

Heat-shock induced nuclear retention and recycling inhibition of importin alpha

Heat-shock induces a strong stress response and modifies all aspects of cellular physiology, which involves dynamic changes in the nucleocytoplasmic distributions of a variety of proteins. Many distinct nucleocytoplasmic transport pathways exist in eukaryotic cells, but how a particular transport pathway is regulated under different cellular conditions remains elusive. The finding of this study indicate that conventional nuclear import, which is mediated by importin alpha/beta, is down-regulated, while the nuclear import of 70 kD heat-shock cognate protein is up-regulated in heat-shock cells. Among the factors involved in the mediation of the conventional nuclear import, significant levels of importin alpha accumulate in the nucleus in response to heat-shock. An analysis of the behaviour of importin alpha with fluorescence recovery after photobleaching and fluorescence loss in photobleaching studies show that nuclear importin alpha becomes less mobile and its nucleocytoplasmic recycling is impaired in heat-shock cells. These data coincided well with biochemical and cytological studies. Our present data show that heat-shock induces the nuclear accumulation, nuclear retention, and recycling inhibition of importin alpha, resulting in the suppression of conventional nuclear import. This suggests a new regulatory mechanism for the adaptation of cells to environmental changes, such as heat-shock.     

Transurethral detachment prostatectomy using a tissue morcellator for large benign prostatic hyperplasia.

OBJECTIVE: Transurethral enucleation of the prostate (TUE) is designed for complete removal of the prostate lobes. On the basis of TUE and holmium laser enucleation of the prostate, we developed a new technique of transurethral detachment prostatectomy (TUDP) using a tissue morcellator. MATERIALS AND METHODS: In TUDP, enucleation is performed with a prostate-detaching blade and the tip of a resectoscope, followed by removal of the tissue with a morcellator. This study reports our experience with TUDP in which the weight of retrieved tissue was greater than 30 g in 76 patients with benign prostate hyperplasia. RESULTS: The mean preoperative total prostate and adenoma volumes were 70.7 and 47.4 mL, respectively. The mean times required for enucleation, morcellation, and total operation time were 28.5, 14.4, and 66.3 minutes, respectively. The mean weight of removed prostate tissue was 61.1 g. The mean decreases in the levels hemoglobin and serum sodium were 1.73 mg/dL and 2.41 mEq/dL, respectively. The mean preoperative maximum flow rate (Qmax), International Prostate Symptom Score (IPSS), and quality of life score (QOL) improved from 9.8 mL/sec, 20.2, and 4.9, to 22.3 mL/sec, 3.1 and 1.2, respectively. Complications included mild morcellator-induced mucosal injury in 2 patients (2.6%), nausea in 4 patients (5.2%), transient urinary retention in 2 patients (2.6%), transient urge incontinence in 5 patients (6.4%), and urethral stricture in 2 patients (2.6%). The mean prostate volume and serum prostate-specific antigen level measured 6 months postoperatively in 46 patients were 10.68 mL and 0.89 ng/mL, respectively. CONCLUSIONS: TUDP is effective for complete removal of large prostate lobes in patients with large benign prostate hyperplasia and is associated with lower perioperative morbidity.     

Loci on murine chromosomes 7 and 13 that modify the phenotype of the NOA mouse, an animal model of atopic dermatitis

The NOA (Naruto Research Institute Otsuka Atrichia) mouse is an animal model of allergic or atopic dermatitis, a condition characterized by ulcerative skin lesions with accumulation of mast cells and increased serum IgE. We reported earlier that a major gene responsible for dermatitis in the NOA mouse lay in the middle of chromosome 14, and that the incidence of disease clearly differed according to parental strain; the mode of inheritance was autosomal recessive with incomplete penetrance. In the study reported here, we searched for genes that might modify the NOA phenotype, and we identified two candidate loci that appeared to contain genes capable of modifying atopic or allergic dermatitis, one in the middle of chromosome 7 (χ² = 14.66; P = 0.00013 for D7Mit62) and the other in the telomeric region of chromosome 13 (χ² = 15.352; P = 0.000089 for D13Mit147). These loci correspond to regions of synteny in human chromosomes where linkages to asthma, atopy, or related phenotypes, such as serum IgE levels, have been documented. Received: December 18, 2000 / Accepted: January 19, 2001     

Clinical evaluation of 430 MHz microwave hyperthermia system with lens applicator for cancer therapy

The clinical efficacy of a microwave (MW) hyperthermia system using an electric-field converging (lens) applicator is evaluated for 42 malignant tumours with a maximum tumour depth of less than 7 cm. The mean of the maximum, average and minimum tumour temperature of the 42 tumours are 44,5, 42.5 and 40.7 C, respectively. The thermal parameters are higher for tumours in the chest, abdominal walls and hip than for those in the neck, groin and extremities. No apparent difference in thermal parameters according to the depth of tumour is shown. Of 40 tumours treated by hyperthermia in combination with radiotherapy, 20 (50%) showed complete regression, 14 (35%) showed partial regression, and six (15%) showed no change. This phase I and II study indicates clinical feasibility of the newly developed MW heating apparatus, and strongly suggests the usefulness of thermoradiotherapy in the treatment of localised superficial and subsurface malignancies.     

Protease inhibitors (gebexate mesylate and ulinastatin) stimulate intracellular chemiluminescence in human neutrophils.

The effect of protease inhibitors on the intracellular production of free radicals was investigated by measuring chemiluminescence (CL) elicited from phagocytosed luminol-bound microspheres (Lumispheres) in human neutrophils stimulated with formylmethionyl-leucyl-phenylalanine (fMLP), interleukin-8 (IL-8), phorbol 12-myristate 13-acetate, or diacylglycerol. Both gabexate mesylate (Foy) and ulinastatin (Miraclid), urinary trypsin inhibitor, increased intracellular CL in a dose dependent manner. Compared to control buffer without protease inhibitor, gabexate mesylate (322 micrograms/ml) caused about a 10-fold increase in intracellular CL in stimulated neutrophils, and ulinastatin (3100 U/ml) a twofold increase in neutrophils stimulated with fMLP or IL-8. When the protease inhibitors were added to the cell suspension after the phagocytosis of lumispheres, CL responses rapidly increased again to the level which was observed when both protease inhibitors and neutrophil stimulants were incubated simultaneously. In contrast, extracellular release of oxygen metabolites from stimulated neutrophils, assayed by a conventional measurement of luminol-dependent CL, was reduced by the protease inhibitors in a dose dependent fashion. When luminol-unbound microspheres were incubated with neutrophils stimulated by fMLP in luminol solution, extracellular CL was almost completely inhibited by gabexate mesylate. These results indicate that the protease inhibitors enhance the generation of intracellular CL and suppress the extracellular release of free radicals.     

Blastocoele collapse by micropipetting prior to vitrification gives excellent survival and pregnancy outcomes for human day 5 and 6 expanded blastocysts

BACKGROUND: Manual puncture of the trophectoderm of human blastocysts with a needle before vitrification increases their survival rate, but the embryos take a long time to re-expand. This study examined whether causing human blastocysts to collapse by manual pipetting before vitrification would allow more rapid re-expansion and improve pregnancy rates. METHODS: After embryo transfer in IVF cycles, surplus embryos that developed to the expanded blastocyst stage were placed in cryoprotectant and then artificially shrunk by mechanical pipetting with a fine hand-drawn glass pipette slightly smaller in diameter than the blastocyst. The shrunken embryos were placed in a small volume of vitrification solution and plunged into liquid nitrogen on a cryotop. The blastocysts were thawed by warming and then dilution in 1 mol/l sucrose. RESULTS: Of 49 expanded vitrified blastocysts, 48 (98%) re-expanded within 3 h after warming. Following transfer (48 blastocysts in 28 cycles), 14 women (50%) became clinically pregnant, and the implantation rate was 33% (16/48). Eight healthy babies have been born in six deliveries, and the other eight pregnancies are ongoing. To date, there have been no spontaneous abortions. CONCLUSIONS: The results suggest that artificial shrinkage with pipetting is a simple and effective technique to assist successful cryopreservation of expanded blastocysts by vitrification.     

A new method using F-waves to measure muscle fiber conduction velocity (MFCV)

OBJECTIVE: First, to propose a new technique for measuring muscle fiber conduction velocity (MFCV). Second, to ascertain the validation of the new method that uses F-waves (F-MFCV) in healthy volunteers. Third, to examine the relationship between F-MFCV and motor nerve conduction velocity (MCV) in the same subjects. SUBJECTS AND METHODS: F-waves reflecting single motor units were recorded with a multi-channel surface electrode array and weak electrical stimulation to the median or ulnar nerves in 21 healthy volunteers. F-MFCVs of the abductor pollicis brevis (APB) and abductor digiti minimi (ADM) were calculated from the F-wave peak latency in each channel. MFCV during minimal voluntary contraction (V-MFVC) was measured in the same muscles. RESULTS: There was no significant difference between F-MFCV and V-MFCV in the muscles tested The mean F-MFCV value was similar to recently reported MFCV values generated by minimal voluntary contraction. No significant differences were found between the APB and ADM F-MFCVs, whereas the MCV of the ulnar nerve was faster than that of the median nerve. CONCLUSION: The MFCV in a single motor unit could be measured with a multi-channel surface electrode array by recording F-waves induced by weak stimulation. Since V-MFCV generated by minimal voluntary contraction is explained by the size principle, V-MFCV reflects small and slow conducting motor unit. There was no significant difference between F-MFCV and V-MFCV. It seemed that F-MFCV also reflected small motor unit. The reason for the lack of difference in the F-MFCVs of the ADM and APB is considered to be a relatively slow F-MFCV. Moreover, MCV reflected the speed of the fastest nerve fiber, whereas F-MFCV did not.     

In vitro activity and beta-lactamase stability of the oral cephalosporin BMY-28100

BMY-28100 was compared with cephalexin, cefaclor, cefixime, and cefteram and found to be more active than the reference cephalosporins against Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus faecalis,and Clostridium difficile.BMY-28100 was the next most active, after cefteram, against Streptococcus pyogenes and Streptococcus pneumoniae.Against gram-negative bacteria, BMY-28100 showed similar activity to that of cefaclor. The antimicrobial activity of BMY-28100, including bactericidal activity, against Staphylococcus aureus was less affected by penicillinase-production than was that of cefaclor. BMY-28100 was more stable than cefaclor against various types of penicillinases, especially against the penicillinase from Staphylococcus aureus.