Calpain 10 and type 2 diabetes: are we getting closer to an explanation?

Purpose Of Review: A variation in the gene encoding the cysteine protease calpain 10 (CAPN10) was recently linked and associated with type 2 diabetes by positional cloning. This positional cloning was a follow-up investigation to the identification of a diabetes-linked region on human chromosome 2 identified by genome-wide scanning a few years earlier. In this paper we give a general background on the genetic studies performed on CAPN10 to date, and review the most recent studies on the functional role of calpain 10.

Overexpression of immediate early genes in active Graves' ophthalmopathy.

Context: In Graves' ophthalmopathy a major problem is an increase in the intraorbital adipose tissue volume.

Objective: The aim of this work was to define mechanisms of orbital adipogenesis.

Design: This was an open-label prospective study.

Haplotype construction of the FRDA gene and evaluation of its role in type II diabetes.

A GAA-repeat in the X25 gene is causing Friedreich's ataxia (FRDA), a common neurodegenerative disease and >20% of FRDA patients develop type II diabetes (T2D). Linkage has previously been detected between T2D and chromosome 9p13-q21, the region that harbours the X25 gene, but association studies of this gene in T2D have been contradicting. Here, we examined whether genetic variation in the X25 gene is associated with risk for T2D.

Magnitude of interference after diphtheria-tetanus toxoids-acellular pertussis/Haemophilus influenzae type b capsular polysaccharide-tetanus vaccination is related to the number of doses administered.

We compared the antibody response to Haemophilus influenzae type b capsular polysaccharide (PRP) after 1, 2, or 3 doses of a diphtheria-tetanus toxoids-acellular pertussis (DTaP) vaccine combined with a PRP-tetanus conjugate (PRP-T) vaccine, followed by separate injections of DTaP and PRP-T vaccines for the last 1 or 2 doses. Healthy infants were recruited from pediatric practices and were immunized according to recommended schedules. A significant decrease in the mean anti-PRP (from 5.

Efficacy of hydrolytic enzymes in preventing radiation therapy-induced side effects in patients with head and neck cancers.

Purpose: Based on in vitro and on clinical evidence of protection against acute side effects of radiation, a prospective randomized, open study was performed to determine the efficacy of an oral proteolytic enzyme preparation in patients with head and neck cancer receiving conventional fractionated radiation therapy.

Methods: Patients with stage T3/T4 head and neck cancer were eligible. One hundred patients from two centres were entered into the study.

Differential effects of IH636 grape seed proanthocyanidin extract and a DNA repair modulator 4-aminobenzamide on liver microsomal cytochrome 4502E1-dependent aniline hydroxylation.

Previous studies from our laboratories have linked the protective abilities of IH636 grape seed proanthocyanidin extract (GSPE) with inactivation of anti-apoptotic gene bcl-XL, and modification of several other critical molecular targets such as DNA-damage/DNA-repair, lipid peroxidation and intracellular Ca2+ homeostasis. Especially, GSPE provided dramatic protection against acetaminophen (APAP)-induced hepatotoxicity, significantly increased bcl-XL expression in the liver, and antagonized both necrotic and apoptotic deaths of liver cells in vivo. However, it was not clear from this study whether anti-apoptogenic and anti-necrotic effects of GSPE were: (i) due to its interference with endonuclease activity, (ii) due to its antioxidant effect, or, (iii) due to its ability to inhibit microsomal drug metabolizing enzyme(s), such as CYP-4502E1.

INDUCTION OF LABOUR WITH MISOPROSTOL - A PROSTAGLANDIN E1 ANALOGUE.

The purpose of our study was to compare the safety and efficacy of intravaginal misoprostol versus existing hospital protocol of intracervical dinoprostone and oxytocin for cervical ripening and induction of labour. 200 patients with indication for induction of labour were randomly assigned to receive either intravaginal misoprostol or dinoprostone/oxytocin combination. In first group twenty five micrograms of misoprostol was placed intravaginally every 6 hours till the patient reached active stage of labour.

Prognosticators of survival in differentiated thyroid carcinoma.

Differentiated carcinoma of the thyroid has good prognosis, even in patients presenting in the late stage and with distant metastasis. In India, the incidence of papillary carcinoma and follicular carcinoma are in the ratio of 60∶40. A retrospective study was carried out to determine the impact of patient and tumor factors on survival, and to develop a simple rish group staging system to predict survival in patients with differentiated thyroid carcinomas.

Absence of a significant interaction between a Haemophilus influenzae conjugate vaccine combined with a diphtheria toxoid, tetanus toxoid and acellular pertussis vaccine in the same syringe and inactivated polio vaccine.

Background: We compared the antibody response to Haemophilus influenzae type b capsular polysaccharide (PRP) after three doses of a diphtheria toxoid, tetanus toxoid and acellular pertussis vaccine (DTaP) combined with a PRP-tetanus conjugate (PRP-T) in infants randomized to receive oral polio vaccine (OPV) or inactivated polio vaccine (IPV). The polio vaccine was given separately at the same visit.

Methods: Three hundred fifty-six infants from pediatric practices in suburban Chicago and New Orleans were randomized into two groups.

A rapid spectrofluorimetric technique for determining drug-serum protein binding suitable for high-throughput screening.

Purpose: To develop and validate a rapid method for determining the dissociation constants with which pharmaceutical candidates and drugs bind to serum albumin and to alpha1-acid glycoprotein with the goal of deducing the extent of binding.

Methods: The quenching of the intrinsic tryptophan fluorescence of serum albumin and alpha1-acid glycoprotein was monitored by spectrofluorimetry and the data were used to calculate the apparent dissociation constant. Sodium warfarin was used to probe the warfarin-binding site of serum albumin and diazepam was used to probe the benzodiazepine binding site.

Rapid Solubility Determination Using Vapor-Phase Osmometry.

Because of the need for resource-sparing assays of the solubility of new drug candidates, we sought to develop and validate a rapid method for determining the solubility of nonvolatile pharmaceutical solids in water. Vapor-phase osmometry was used to determine the concentration of drugs in saturated solutions prepared by a rapid ultrasound-mediated dissolution protocol. The osmolality of saturated solutions as measured by the vapor-phase osmometer is an excellent predictor of the solubility of pharmaceutical solids in water.

Evaluation of an alternative to the Kolmogorov-Smirnov test for flow cytometric histogram comparisons.

Background: The Kolmogorov-Smirnov test is a valid statistical test for comparing distributions that has been recommended for flow cytometric histogram analysis. However, this test is frequently found to be too sensitive for flow cytometric histogram comparisons. Here, a parametric alternative to the Kolmogorov-Smirnov test is proposed that is based on fitting suitable models to flow cytometric data.

Surgery in early cancer of the oral tongue (Tl-2). Wide excision versus hemiglossectomy.

Cancer of the oral tongue is a common disease. Thirty five (35%) percent of patients seen at our hospital are in Stages I&II. The choice of surgical treatment is a wide excision of the lesion (WE) or a hemiglossectomy (HG).

EARLY CARCINOMA TONGUE - SURGICAL OPTIONS.

A retrospective analysis of 127 surgically treated cases of T-1, T-2 carcinoma of oral tongue during the period 1987-1990 was undertaken. 68.5 per cent (87) underwent hemiglossectomy and 31.

CO LASER - A NEW TOOL IN THE SURGEONS ARMAMENTARIUM.

One hundred and sixty five patients, treated with carbondioxide (CO) laser for benign and malignant lesions of the head and neck were studied. Alveolo-buccal complex (68/165) had the majority of benign and malignant tumors followed by larynx (23/165) and tongue (21/165). All lesions were widely excised, none were reconstructed and all defects healed well with minimal scarring.

Histologic trends in thyroid cancer 1969-1993: a clinico-pathologic analysis of the relative proportion of anaplastic carcinoma of the thyroid.

Background: It was observed that new presentations of anaplastic carcinoma of the thyroid had become infrequent in the last two decades.

Methods: All cases of thyroid cancer seen at our centre between 1969-1993 (n = 2921) were classified as papillary 49%, follicular 34%, medullary 7.5%, anaplastic 4.

Long-term follow-up of patients with meningiomas involving the cavernous sinus: recurrence, progression, and quality of life.

Objective: In this report, we evaluate the recurrence- and progression-free survival of patients with meningiomas involving the cavernous sinus.

Methods: The rates of tumor recurrence and progression in 119 patients with meningiomas involving the cavernous sinus treated between 1983 and 1993 were analyzed.

Results: The mean follow-up period was 33.

Prognostic factors in follicular carcinoma of the thyroid: a study of 198 cases.

Background: Prognostic parameters for papillary carcinoma of the thyroid have been defined by several groups. However, no such study has been reported for follicular carcinoma.

Methods: We undertook a retrospective study of well-differentiated carcinoma of the thyroid operated at the Tata Memorial Hospital during the period 1970-1985.

Laryngectomy: a quality of life assessment.

Cosmetic disfigurement and loss of voice following a total laryngectomy can cause major psychosocial problems. Fifty patients who had undergone a total laryngectomy and completed more than six months following surgery, were randomly selected during a routine follow-up, and asked to answer a questionnaire, to asses their degree of disability and extent of rehabilitation. The questionnaire have five main components viz.

Extent of lymph node dissection in T3/T4 cancer of the alveolo-buccal complex.

Background: Cancer of the alveolo-buccal complex even when locally advanced is amenable to curative resection. However, the extent of lymph node dissection remains controversial.

Methods: A total of 181 patients with T3/T4 cancer of the alveolo-buccal complex who underwent a radical neck dissection (RND) were analyzed retrospectively to determine the incidence and pattern of lymph node involvement and to define the extent of neck dissection required in these cancers.

Organization, sequence and regulation of expression of the murine Hoxa-7 gene.

The genomic sequence of Hoxa-7 (encoding the HOXa-7 homeobox protein), including the coding region (0.7 kb), flanked by a 5'-upstream region (2.8 kb), a 3'-downstream region (1 kb) and interrupted by an intron (995 bp), was determined.

Perioperative chemotherapy in patients with oral cancer.

In the final report of a prospective, randomized controlled clinical trial, we report the results of using adjuvant perioperative chemotherapy in patients with oral cancer. Our study is based on the hypothesis of Goldie and Coldman. A total of 135 patients with alveolobuccal carcinoma, classified as clinically stage III and IV, were entered on the protocol.