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Biomedical subjects

S Bhatti

Publications and source records attributed to S Bhatti.

At least 19 recordsLinked to original sources
PubMed2006

Efficacy of isoniazid prophylaxis in renal allograft recipients.

The efficacy of isoniazid (INH) prophylaxis in renal allograft recipients who are on long-term immunosuppression in a region highly prevalent for tuberculosis (TB) was studied. INH (300 mg/d in patients weighing more than 35 kg and 5 mg/kg/d in patients with <35 kg body weight) together with Pyridoxine 50 mg/d for 1 year was started in randomly assigned renal allograft recipients. Occurrence of clinical tuberculosis during the initial 2 years posttransplantation was observed in the risk group and patients at no risk. Risks were defined as acute rejection episodes and exposure to antirejection therapy, past history of TB completely or incompletely treated, radiological evidence of past tuberculosis, history of tuberculosis in close contacts. Among 480 patients registered in the study, INH prophylaxis was given to 219 randomly assigned renal allograft recipients. Results were compared among patients developing TB during the initial 2 years posttransplantation in both the groups. Risk factors were analyzed for comparison in both groups. No significant difference was observed in terms of past history of TB, TB in close contacts, episodes of acute rejection during the initial 3 months, and comorbidities such as cytomegalovirus infection, hepatitis C virus infection, and posttransplant diabetes. One patient from the INH group and 10 patients from the non-INH group developed TB during the initial 2 years posttransplantation (P < .0001). None of patients required discontinuation of INH. INH was observed to be safe and effective as a chemoprophylactic agent in renal allograft recipients.

Antitubercular Agents↗
PubMed2006

Laryngeal paralysis-polyneuropathy complex in young related Pyrenean mountain dogs.

OBJECTIVES: To characterise clinical, electrophysiological and histopathological findings. To analyse pedigree information in six young related Pyrenean mountain dogs with laryngeal paralysis-polyneuropathy complex (LP-PNC). METHODS: A retrospective study of clinical records and pedigrees of six young related Pyrenean mountain dogs with LP-PNC was carried out. RESULTS: All dogs were presented with laryngeal paralysis and concurrent megaoesophagus. Electrodiagnostic testing was performed in three dogs and showed electrophysiological abnormalities in the distal appendicular muscles. Histopathological findings of peripheral nerve samples were dominated by distal axonal degeneration. Clinical, electrophysiological and histopathological findings were supportive of a diagnosis of degenerative, sensorimotor LP-PNC, similar to that reported in young dalmatians and rottweilers. All dogs died or were euthanased by two years of age. An autosomal recessive mode of inheritance was suspected based on pedigree analysis. CLINICAL SIGNIFICANCE: Congenital LP-PNC should be suspected in any young dog presenting with laryngeal dysfunction and other concurrent neurological abnormalities. The prognosis is usually poor.

Animals↗
PubMed2005

Calcinosis involving multiple paws in a cat with chronic renal failure and in a cat with hyperthyroidism.

Calcinosis of multiple paws is described in two cats. A metastatic pathogenesis was supported by the laboratory findings of hyperphosphataemia and a calcium x phosphorus solubility product > 7 g/L. Hyperparathyroidism could not be confirmed because a valid feline parathyroid hormone assay was not available at the time. One cat was diagnosed with chronic renal failure and presented initially with an irregular nodular calcification on the chin. Dietary and medical management was unsuccessful and ultimately the animal was euthanased. Hyperthyroidism was diagnosed in another cat by laboratory findings and scintigraphic imaging. In addition, the cat had a hyperphosphataemia in the absence of azotaemia. Intravenous administration of radioactive iodine as (131)I was accompanied by reduction and normalization in serum total thyroxine and phosphorus concentrations and resulted in resolution of calcification in the paws.

Animals↗
PubMed2005

Sensory neuropathy in two Border collie puppies.

A peripheral sensory neuropathy was diagnosed in two Border collie puppies. Neurological, electrophysiological and histopathological examinations suggested a purely sensory neuropathy with mainly distal involvement. Urinary incontinence was observed in one of the puppies and histological examination of the vagus nerve revealed degenerative changes. An inherited disorder was suspected.

Animals↗
PubMed2004

'Continuous muscle fibre activity' in six dogs with episodic myokymia, stiffness and collapse.

Continuous muscle fibre activity was observed in a crossbred dog, a Yorkshire terrier, a border collie and three Jack Russell terriers. The clinical signs consisted of episodes of generalised myokymia which developed into muscle stiffness and delayed muscle relaxation and generally led to the dogs collapsing into lateral recumbency. These episodes were preceded by intense facial rubbing in three of the dogs, and were associated with severe hyperthermia in five of them. All three Jack Russell terriers showed continuous ataxia. The dogs had above normal activities of aspartate aminotransferase, alanine aminotransferase and creatine kinase, but their cerebrospinal fluid was normal. Myokymic discharges were observed by electromyography in two of the dogs. Two of them were treated with membrane-stabilising agents, with variable results.

Animals↗
PubMed2001

Atlantoaxial cartilaginous exostosis causing spinal cord compression in a mature Bernese mountain dog.

Cartilaginous exostosis developed in the atlantoaxial region of a three-and-a-half-year-old Bernese mountain dog. The dog exhibited ataxia in the hindlimbs and flailing movements in the forelimbs. On survey radiographs of the cervical spine there was a focal calcified mass between the dorsal arch of the atlas and the spinous process of the axis. Lumbar myelography revealed severe dorsal spinal cord compression. The mass was removed surgically and the dog made a complete recovery. Histopathology of the excised mass was consistent with a diagnosis of cartilaginous exostosis.

Animals↗
PubMed1999

The effect of bile salts and calcium on isolated rat liver mitochondria.

Intact mitochondria were incubated with and without calcium in solutions of chenodeoxycholate, ursodeoxycholate, or their conjugates. Glutamate dehydrogenase, protein and phospholipid release were measured. Alterations in membrane and organelle structure were investigated by electron paramagnetic resonance spectroscopy. Chenodeoxycholate enhanced enzyme liberation, solubilized protein and phospholipid, and increased protein spin label mobility and the polarity of the hydrophobic membrane interior, whereas ursodeoxycholate and its conjugates did not damage mitochondria. Preincubation with ursodeoxycholate or its conjugate tauroursodeoxycholate for 20 min partially prevented damage by chenodeoxycholate. Extended preincubation even with 1 mM ursodeoxycholate could no longer prevent structural damage. Calcium (from 0.01 mM upward) augmented the damaging effect of chenodeoxycholate (0.15-0.5 mM). The combined action of 0.01 mM calcium and 0.15 mM chenodeoxycholate was reversed by ursodeoxycholate only, not by its conjugates tauroursodeoxycholate and glycoursodeoxycholate. In conclusion, ursodeoxycholate partially prevents chenodeoxycholate-induced glutamate dehydrogenase release from liver cell mitochondria by membrane stabilization. This holds for shorter times and at concentrations below 0.5 mM only, indicating that the different constitution of protein-rich mitochondrial membranes does not allow optimal stabilization such as has been seen in phospholipid- and cholesterol-rich hepatocyte cell membranes, investigated previously.

Animals↗
PubMed1997

C-terminal isoforms of the myosin heavy chain and smooth muscle function.

Two myosin heavy chain isoforms expressed in smooth muscle, SM1 (204 kDa) and SM2 (200 kDa), are derived from alternate splicing that results in different amino acid sequences at their non-helical C-terminal tail regions. These isoforms are developmentally regulated and differentially expressed in various smooth muscle tissues. The functional role of myosin isoforms differing at the C-terminal tail has been investigated both in vitro and in vivo. Removal of the C-terminal tail of SM1 by chymotrypsin activates the ATPase of myosin at low Mg2+ but does not change the maximum activity. Addition of peptides, mimicking C-terminal tail regions specific to the SM1 and SM2 isoforms, to permeabilized taenia coli smooth muscle fibers inhibits maximum shortening velocity (Vm) and decreases Ca2+ sensitivity but has no effect on maximum force. The inhibition of Vm by the SM1-peptide was not reversed on washout, whereas Vm inhibition by the SM2-peptide is reversible. We demonstrated that the SM1 peptide specifically bound to myosin at the subfragment 2-light meromyosin (S2-LMM) junction using crosslinking and immunomicroscopy. Modification at this site could have a direct effect on crossbridge function. The relation between C-terminal myosin isoforms and contractile function in vivo was examined using estrogen administration to ovariectomized rats to increase the relative expression of the SM1 C-terminal isoform in uterine smooth muscle. This increase in SM1 was significantly correlated with an increase in Vm. In contrast, the high ATPase N-terminal isoform was decreased by administration of estrogen to ovariectomized rats. Thus, changes in C-terminal isoform distribution appear to affect contractile function in vivo. We propose a mechanism whereby the interactions between the C-terminal tail of one myosin molecule and the S2-LMM region of another in the thick filament can modulate contractility in an isoform specific manner. Further work is needed to unequivocally identify the function of smooth muscle myosin isoforms. However, our evidence suggests that the C-terminal heavy chain isoforms may be important modulators of smooth muscle contractility.

Amino Acid Sequence↗
PubMed1996

Ursodeoxycholic acid and prednisolone versus ursodeoxycholic acid and placebo in the treatment of early stages of primary biliary cirrhosis.

BACKGROUND: Ursodeoxycholic acid probably is not able to cure primary biliary cirrhosis. Therefore in this study ursodeoxycholic acid was administered together with prednisolone, since monotherapy with glucocorticoids has been shown to have some positive effects. METHODS: Thirty patients with primary biliary cirrhosis (stages I-III) were entered into the study. Fifteen were treated with ursodeoxycholic acid 10 mg.kg-1.day-1 and placebo (group A), 15 with ursodeoxycholic acid and 10 mg prednisolone (group B) for 9 months. Apart from the usual laboratory examinations, liver biopsies were taken from 29 patients before and after therapy. RESULTS: Liver enzymes decreased significantly compared to the initial values in both groups (p < 0.001), but in group B cholestasis-indicating enzymes and the immunoglobulins G and A improved more rapidly. Between both groups the differences for AP, GGT, IgG, IgA and gamma-globulins were significant (p < 0.05), but only for short terms. In group B, liver histology improved significantly (p < 0.003), which correlated with the decrease of IgG. Ursodeoxycholic acid became the predominant bile acid in the serum. Toxic bile acids did not increase. Bone densitometry revealed a slight deterioration of preexisting osteoporosis in one patient. CONCLUSIONS: Although combination therapy with ursodeoxycholic acid and prednisolone was not superior to monotherapy with ursodeoxycholic acid with regard to liver function tests, it had a highly beneficial influence on liver histology. In our previous trials with monotherapy histology remained unchanged. An early decrease in IgG during combination therapy seems to be an indicator of an amelioration of liver histology.

Adult↗
PubMed1996

The care of older persons with diabetes mellitus: families and primary care physicians.

OBJECTIVES: To determine the extent to which family members participate in the day-to-day management of diabetes mellitus in older persons, and in older diabetics' medical encounters, and to identify patient and family member characteristics associated with this participation. DESIGN: A longitudinal observational study, with baseline data being reported herein. SETTING: Three primary care practice settings in Seattle, Washington, Boston, Massachusetts, and Indianapolis, Indiana. PARTICIPANTS: Family members of patients 70 years of age or older participating in the Patient Outcomes Research Team (PORT) Study of type II diabetics. MAIN OUTCOME MEASUREMENTS: The two dependent variables represent, respectively, the extent of family members' assistance with diabetes-related care and participation in older diabetics' medical encounters. RESULTS: The 357 family members enrolled were older (mean age = 66.3 years), were mostly women (76.2%), and were usually the spouses of diabetic patients (71.3%). Between 22% and 50% of family members reported helping with various aspects of diabetes care; 35.6% of family members participated regularly in their diabetic patients' medical encounters. A multiple linear regression model relating family assistance with diabetes-related care to patient and family member characteristics included four variables: patients' physical function, and the family member's relationship to the patient, assistance with basic activities of daily living (ADLs), and understanding of diabetes management issues (all P < .05). A multiple logistic regression model relating family member participation in the medical encounter to patient and family member characteristics also included four variables: patient age and physical function, and family member assistance with instrumental activities of daily living (IADLs) and with diabetes-related care (all P < .05). CONCLUSION: The family members studied frequently assisted older diabetics with diabetes-specific care; more than one-third were regular participants in older diabetics' medical encounters. Family member involvement in the day-to-day management of diabetes and in the medical encounter was more likely when patients were functionally disabled. Health care systems and physicians need to educate their older patients, and involved family members when patients are frail, about diabetes-related care issues and support them in their roles in the management of diabetes as well as other chronic diseases.

Activities of Daily Living↗
PubMed1996

Acute renal failure due to traumatic rhabdomyolysis.

Between 1990 and 1993, we studied 14 cases of acute renal failure due to prolonged muscular exercise (e.g., squat jumping, sit-ups) and blunt trauma inflicted by law enforcement personnel using sticks or leather belts. None of the patients had a prior history of myopathy, neuropathy, or renal disease. All were critically ill and required renal support in the form of dialysis. Although the morbidity was high, 13 of the patients recovered normal renal function. One patient expired due to sepsis.

Acute Kidney Injury↗
PubMed1995

Predicted disulfide-bonded structures for three uniquely related proteins of Plasmodium falciparum, Pfs230, Pfs48/45 and Pf12.

Pfs230 is a surface protein of the gametes of Plasmodium falciparum and has been demonstrated to be a target of malaria transmission-blocking antibodies; it is an important candidate antigen for a transmission-blocking vaccine. The target epitopes of transmission-blocking antibodies against Pfs230 are almost all reduction sensitive suggesting that disulfide bonds are critical for folding the native molecule. Following the cloning of the Pfs230 gene attempts are now underway to express subunits of the protein for use in vaccine trials. It will be important to understand the disulfide-bond structure of the Pfs230 to achieve this goal. In this paper we present a model for this structure based on the observation that the Pfs230 molecule contains a series of regularly repeated cysteine-containing motifs. Four such motifs have been identified, together with a fifth cysteineless motif, which occur in the same relative order, with regular alternating omission of specific motifs, 14 times throughout the length of the protein. Each of the 14 sets of motifs contains an even number of cysteine residues (2, 4 or 6). We postulate that each set folds into a separate disulfide-bonded domain in which corresponding pairs of cysteines form an equivalent disulfide bond in every such domain. The postulated bonding arrangements in the different domains are mutually confirmatory throughout the sequence of Pfs230. We have identified two other malaria proteins, Pfs48/45 and Pf12, which share the same arrangements of motifs and conform to the same disulfide-bond structure proposed for Pfs230; no other proteins in the sequence data base share these characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

COS cell expression cloning of Pfg377, a Plasmodium falciparum gametocyte antigen associated with osmiophilic bodies.

We report the deduced protein sequence and preliminary characterization of Pfg377, a novel sexual stage antigen of Plasmodium falciparum. An initial cDNA clone (Pfg377-1) encoding the N-terminal 755 amino acids of Pfg377 was isolated by transfecting a 3D7 gametocyte cDNA library into COS7 cells and selecting using a pool of anti-Pfs230 monoclonal antibodies. The protein encoded by Pfg377-1 included an N-terminal hydrophobic signal sequence, but no apparent transmembrane anchor. Instead, the particular cDNA clone selected was fused in-frame at its 3' end with the coding sequence for the human decay acceleration factor membrane anchor, which had been deliberately placed downstream of the vector polylinker in order to attach potential fusion proteins onto the COS cell surface. Northern blots probed with the Pfg377-1 cDNA demonstrated cross-hybridization to a single approximately 9.5-kb transcript, which was present only in sexual stages, and not in a sexual stages. DNA hybridization was used to obtain a series of overlapping genomic clones which collectively yielded the complete DNA sequence for Pfg377. There are no introns within the gene, which contains a 9360-bp open reading frame and encodes a 377-kDa protein. The Pfg377 protein is highly hydrophilic, and has an essentially non-repetitive structure, with only four very limited regions of tandem repeats. The Pfg377 gene resides on chromosome 12, and immunoelectron microscopy with two different anti-Pfg377 polyclonal antisera raised against two separate recombinant sub-fragments of the protein both indicated that the antigen is located in electron-dense organelles of the gametocytes--the osmiophilic bodies--which are proposed to play a role in parasite emergence from the erythrocyte during gametocyte maturation in the Anopheles mosquito midgut. Although it was selected with anti-Pfs230 antibodies, comparison of the sub-cellular locations and protein sequences of Pfg377 and Pfs2 show them to be completely distinct antigens. We hypothesize that Pfg377-1 was initially isolated because it expresses an epitope which is recognized by (i.e., cross-reacts with) one of the anti-Pfs230 monoclonal antibodies used to select the original transfected COS cells.

Amino Acid Sequence↗
PubMed1995

TUDCA and UDCA are incorporated into hepatocyte membranes: different sites, but similar effects.

The aim of this paper is to point out that: 1) CDCA and DCA increase the polarity of cell membranes and cause the release of cholesterol and phospholipid from the membranes; 2) the extent of this damage is inversely correlated with the cholesterol content of the membrane investigated; 3) UDCA, TUDCA and GUDCA decrease membrane polarity; 4) they prevent membrane damage when added prior to CDCA or DCA; 5) UDCA appears to be incorporated into the apolar domain of the membrane, TUDCA, GUDCA into the interface; 6) UDCA decreases HLA class I expression on hepatocyte membranes; 7) CDCA induces GLDH-release from liver mitochondria and increases mitochondrial membrane polarity and mobility; and 8) UDCA reduces the release of GLDH from mitochondria caused by CDCA.

Animals↗