We established a diagnosis of familial amyloidotic polyneuropathy (FAP) based on DNA and demonstrated a direct link between prealbumin gene mutation and FAP. The individuals with FAP, so far ...examined, were heterozygous for the prealbumin gene, carrying one normal and one mutant gene. To investigate the molecular pathogenesis of FAP, we isolated a normal prealbumin gene (7 kb in length) and also a mutant prealbumin gene associated with FAP. We compared their nucleotide sequences and found that they matched except for a single-base substitution present in the second exon. In an effort to construct mouse model systems for the FAP, we developed strains of transgenic mice carrying human mutant prealbumin genes.
ABSTRACT
We studied the effects of milk basic protein (MBP) on bone metabolism in ovariectomized (OVX) rats. Five‐week‐old female Sprague‐Dawley rats were ovariectomized and fed a low‐calcium diet ...(0.009% Ca) for 5 weeks. The OVX rats were divided into three experimental groups: Control group (20% casein), MBP‐L group (19.9% casein, 0.1% MBP), and MBP‐H (19% casein, 1% MBP) of six animals. The rats were fed each experimental diet for 3 weeks. The bone breaking strength and energy of femur in the MBP‐H group were significantly higher than those in the control group. The bone breaking energy of femur in the MBP‐L group was also significantly higher than those in the control group. There were no differences in the amount of femoral calcium and phosphorus among the three groups, however, the amounts of femoral proline, hydroxyproline and hydroxylysine (typical amino acids of collagen) in the MBP groups were significantly higher than those in the control group. These data indicate that MBP in the whey protein increases the amount of the bone collagen and enhances the bone strength.
Mechanism of carcinogenesis in familial tumors Tamura, Kazuo; Utsunomiya, Joji; Iwama, Takeo ...
International journal of clinical oncology,
08/2004, Volume:
9, Issue:
4
Journal Article
Peer reviewed
It is thought that malignant tumors occur through interactions of multiple environmental factors and a personal genetic factor. A normal somatic cell having an intrinsic function is able to acquire ...the characteristics of a malignant cell under the influence of many factors. A small percentage of all tumors have obvious familial aggregation. These entities are called familial cancer. The familial cancer syndrome is well defined for colorectal cancer, breast cancer, endocrine neoplasia, and so on. Traits of familial tumors are sequentially inherited by offspring through gametes in a Mendelian fashion, most commonly in an autosomal-dominant manner. Carcinogenesis requires multiple genetic events. A patient with a familial tumor is ahead of an individual without any germline mutation in the carcinogenesis process. In such a situation, patients frequently suffer from multiple malignant tumors at a young age. It is well known that three major genes are closely related to the cell cycle and tumorigenesis. These gene types are protooncogenes, tumor suppressor genes, and DNA mismatch repair genes. Proto-oncogenes function to accelerate cells during the G1 or growth phase of the cell cycle. Tumor suppressor genes act as blocks against cell growth and proliferation. Inactivation of tumor suppressor genes requires alterations in both alleles. These phenomena are known as Knudson's two-hits theory. However, DNA mismatch repair genes are known as caretaker genes and correct mismatch pair generation during DNA replication. Germline mutation of DNA mismatch repair genes causes hereditary nonpolyposis colorectal cancer. The tumor phenotype from patients with hereditary nonpolyposis colorectal cancer is demonstrated to be microsatellite instability positive.
We studied the effects of whey protein (WP) and fractionated WP (HWP; heat-stable WP, LWP; low M.W. WP, EWP; ethanol-precipitated WP) on calcium and bone metabolism in ovariectomized (OVX) rats. ...Six-week-old female Sprague-Dawley rats were ovariectomized and fed a low-calcium diet (0.03% Ca, 0.3% P) for 4 weeks. The rats were divided into five groups, Cont, WP, HWP, LWP and EWP group, and were fed a Cont diet (20% casein, 0.3% Ca) or a diet (19% casein, 0.3% Ca) containing 1% WP, HWP, LWP or EWP for 4 weeks. There were no significant differences in the calcium balance, serum calcium and calcitonin levels among the experimental groups. However, serum ALP activity of the HWP and EWP groups at 14 wks. were lower than that of the Cont group. The bone breaking strength and energy of femur of the HWP, LWP and EWP groups were higher than those of the Cont group. As for the amount of calcium, phosphorus, and magnesium in the femur, there were no significant differences among the experimental groups; however, the amounts of total amino acids in the femur of the HWP, LWP and EWP groups were higher than that of the Cont group. The amounts of proline and hydroxyproline (typical amino acids of collagen) in the femur of the HWP, LWP and EWP groups were also higher than those of the Cont group. These data indicate that milk WP contains active components that influence bone metabolism in OVX rats by increasing in bone protein such as collagen and enhance the bone breaking force (strength and energy). These results suggest that the active components are existed in heatstable, low M.W. and 30–70% ethanol-precipitated fraction, respectively.
We have isolated and characterized a cDNA and the gene of the human homologue of CAAF1, a novel member of the S100 calcium-binding protein family. The 276-bp open reading frame encoded a 92-amino ...acid polypeptide with a predicted molecular mass of 10,575 Da. The deduced amino acid sequence of human CAAF1 showed 66% homology to bovine CAAF1. The human CAAF1 gene consisted of three exons, with the two EF hand motifs of the CAAF1 protein separately encoded by exons 2 and 3. This gene was expressed at a high level in polymorphonuclear leukocytes and at an intermediate level in esophageal mucosa. The tissue distribution of CAAF1 mRNA was different from that of other S100 proteins. Direct R-banding fluorescence in situ hybridization revealed that the human CAAF1 gene was mapped to chromosome 1q21.2-q22, where most of the S100 genes form a cluster.
Pharmacokinetic, bacteriological and clinical studies on SY5555, a new oral penem, were carried out, and the following results were obtained. 1. MICs were determined for 6 drugs, SY5555, clavulanic ...acid/amoxicillin (CVA/AMPC), cefaclor (CCL), cefotiam (CTM), cefpodoxime (CPDX), cefdinir (CFDN) against 20 strains of bacteria isolated from patients who were subsequently treated with SY5555. MICs of SY5555 for Gram-positive cocci ranged from 0.05 to 0.10 microgram/ml against 10 strains of Staphylococcus aureus. The MIC was < or = 0.025 microgram/ml against one strain of Streptococcus pyogenes, and MICs were from < or = 0.025 to 0.39 microgram/ml against Streptococcus pneumoniae. These MIC values were equivalent or superior to those of the other 5 drugs. MICs of SY5555 for Gram-negative bacilli were 0.39 and 6.25 micrograms/ml against Haemophilus influenzae, and these values were equivalent to those of the other drugs, except CPDX. The MIC of SY5555 was 0.39 microgram/ml against 2 strains of Escherichia coli, and this value was equivalent or superior to those of CVA/AMPC and CCL, similar or inferior to those of CPDX and CFDN, and inferior to that of CTM. The MICs of several drugs were determined for 10 strains of Bordetella pertussis and 30 strains of Campylobacter jejuni isolated from patients before this clinical study. The MICs of SY5555 against the 10 strains of B. pertussis were compared with those of 7 drugs, CCL, CTM, CPDX, ampicillin (ABPC), piperacillin (PIPC), imipenem (IPM) and erythromycin (EM). The MIC of SY5555 was 0.78 microgram/ml against all of the strains. This value was superior to those of CCL, CTM and CPDX, similar or inferior to that of IPM and inferior to those of PIPC and EM. The MICs of SY5555 against the 30 strains of C. jejuni were compared with those of 7 drugs. CCL, CTM, CPDX, CFDN, ABPC, IPM and EM, and the MIC of SY5555 was < or = 0.025 microgram/ml or 0.05 microgram/ml and these values were equivalent or superior to those of the 7 reference drugs. 2. SY5555 dry syrup was administered orally at 30 min. after meals, to a total of 5 patients, at doses of 5.0 and 10.0 mg/kg to 2 patients each and at a dose of 15.0 mg/kg to one patient and the plasma concentrations were determined. Peak concentrations were detected 1 to 3 hours after administration in all patients and the peak concentrations were 0.93 and 1.21 micrograms/ml at the 5.0 mg/kg dose, 2.85 and 5.49 micrograms/ml at the 10.0 mg/kg dose and 5.79 micrograms/ml at the 15.0 mg/kg dose.(ABSTRACT TRUNCATED AT 400 WORDS)
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