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Biomedical subjects

K M Chan

Publications and source records attributed to K M Chan.

At least 19 recordsLinked to original sources
PubMed1993

Asynchronous reformation of individual kallikrein-related secretory proteinases in rat submandibular glands following degranulation by cyclocytidine.

Time scales for the reformation of the secretory granules in granular tubules and their constituent proteinases were assessed after inducing a massive degranulation by intraperitoneal injection of cyclocytidine in conscious animals. The minimum working dose of cyclocytidine to produce the maximum degranulation and depletion of proteinase activity, at 3 h after injection, was 75 mg/kg. Histologically, although most granular tubule cells then appeared to be extensively degranulated, isolated individual cells showing little or no degranulation always persisted. Acinar cells also showed some depletion of secretory material. At 15 h after injecting cyclocytidine the formation of new granules had begun in the granular tubule cells, but it was not extensive or uniform in adjacent cells; however, the acinar cells already appeared to be regranulated. The pattern of granule reformation in granular tubule cells progressed gradually, so that 7-10 days after cyclocytidine-induced degranulation the cells were mostly packed with granules and showed similar appearances to those of normal resting control glands. Individual proteinases in extracts of the glands were assayed specifically using fluorogenic oligopeptide amidase substrates, with and without appropriate inhibitors. This revealed a 95% reduction in total proteinase activity 3 h after cyclocytidine (75 mg/kg). In the same extracts, acinar peroxidase was reduced by 28%. Peroxidase levels recovered to control values within 15 h after cyclocytidine but recovery of proteinases progressed more gradually and did not occur uniformly for the different constituent proteinases. Tissue kallikrein (rK1) showed the most rapid recovery and had reached levels approaching normal within 3 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Ancitabine↗
PubMed1992

P-glycoprotein genes in the winter flounder, Pleuronectes americanus: isolation of two types of genomic clones carrying 3' terminal exons.

In mammals, P-glycoprotein (P-gp) is encoded by two or more highly conserved genes that differ in their abilities to transport drugs. One isoform class (class I) is consistently associated with the multidrug resistance phenotype, while the other (class III) is not. This study was designed to enumerate the P-gp genes in fish and determine how they are related to the two functional classes already defined in mammals. Southern blot analysis using a conserved single exon from the 3' terminal region of hamster P-gp cDNA (pEX1-172) as a probe indicated that there were two P-gp genes in right-eye flounders. Subsequently, two sets of clones were isolated from a winter flounder genomic library that correspond to the 3' ends of the two flounder P-gp genes. Sequence analysis was done on two key areas: the 3' ATP binding site and the 3' terminal exon, both of which were found to be homologous with their mammalian counterparts. Despite high levels of sequence identity in the predicted coding regions of the gene fragments it has not been possible to use these sequences to relate the homologs to particular mammalian classes of P-gp genes, perhaps because of gene conversion between mammalian P-gp genes. These cloned sequences are the first set of P-gp genes reported in lower vertebrates and will be useful for delineating the expression of P-gp genes in fish and understanding the role of P-gp in fish physiology.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

New specific assays for tonin and tissue kallikrein activities in rat submandibular glands. Assays reveal differences in the effects of sympathetic and parasympathetic stimulation on proteinases in saliva.

At least fourteen separate bands of proteinase activity, labelled A-N, were identified by an enzyme overlay membrane technique, using oligopeptide-7-amino-4-trifluoromethylcoumarin (AFC) substrates in rat submandibular gland extracts fractionated on pH 4-6.5 isoelectric focusing gels. The proteinases were eluted into an ammonium bicarbonate buffer pH 9.8 containing 0.1% Triton X-100 and the relative contribution of each band to total activity evaluated using D-Val-Leu-Arg-AFC (DVLR-AFC) and Z-Val-Lys-Lys-Arg-AFC (ZVKKR-AFC) as substrates. Immunoblotting of band eluants run on sodium dodecyl sulphate gels with antibodies showed that band A was identical with tonin and bands K-N contained tissue kallikrein. Tonin was found to hydrolyse ZVKKR-AFC but not DVLR-AFC. Estimates of the Km values of tissue kallikrein for DVLR-AFC and tonin for ZVKKR-AFC were found to be similar (approx. 20 microM) yet the former enzyme hydrolysed its substrate five times faster. Tonin was inhibited by soybean trypsin inhibitor (SBTI) but not by aprotinin. Tissue kallikrein, on the other hand, was inhibited by aprotinin but was considerably more resistant to inhibition by SBTI. In tissue extracts 95% of the ZVKKR-AFC lytic activity in the presence of 1 microM aprotinin is due to tonin and a similar percentage of the DVLR-AFC hydrolysing activity in the presence of 10 microM SBTI is due to tissue kallikrein. These findings were used for the specific measurement of these two proteinases in submandibular gland extracts and in saliva without prior purification. Using these inhibitor based assays we revealed qualitative differences in the composition of proteinases secreted into saliva during parasympathetic versus sympathetic stimulation of the submandibular gland. The distribution of proteinases in sympathetic saliva is very similar to that found in submandibular extracts but on parasympathetic stimulation, although much less proteinase is released, the contributions of the more acidic isomers of tissue kallikrein are increased and that of tonin and other proteinases dramatically decreased. The data suggest that parasympathetic and sympathetic nerves induce proteinase secretion via different pathways.

Amino Acid Sequence↗
PubMed1992

Secretory oedema in diabetic submandibular glands during parasympathetic nerve stimulation: relationship to microvascular abnormalities in streptozotocin-treated rats.

1. Submandibular secretion during parasympathetic stimulation (5 Hz) was examined in streptozotocin-diabetic and age-matched control rats. 2. At 3 weeks, but not 3 and 6 months, flow rate was initially greater than in controls, but it declined rapidly after 30 min. 3. The reduction in flow rate was associated with oedema of the gland. 4. At 3 months, graded stimulation revealed a tendency to oedema at frequencies of 10 Hz and above. 5. Morphologically, submandibular capillary density was increased in diabetic rats. 6. Thus, in diabetes the submandibular gland appears less able to withstand continuous parasympathetic stimulation, due in part to an increase in tissue capillary area.

Animals↗
PubMed1992

Epilepsy--another cause of intermittent fever with confusion.

The problem of recurring episodes of fever and confusion in an 83 year old man was found to be due to epilepsy. He was treated with carbamazepine which abolished the attacks. Epilepsy-induced fever is a difficult diagnosis to make, and electroencephalogram can be invaluable in making the diagnosis.

Aged↗
PubMed1992

Fracture of the tibial spine in adults and children. A review of 31 cases.

We reviewed 19 adults and 12 children who had been treated for avulsion fractures of the tibial spine. Adult injuries have not previously been reported at length; most were caused by road-traffic accidents, and 68% were associated with other injuries, of which 58% were around the knee. The higher incidence of associated injuries in adults as compared with children, indicates that the injury is the result of greater energy and perhaps a different mechanism. The worse outcome in some adults was due to other associated intra-articular fractures and tears of the medial collateral ligament. Arthroscopy is useful in both diagnosis and treatment. Early accurate diagnosis and the correct treatment produce a good outcome.

Adolescent↗
PubMed1992

Urinary symptoms and urodynamic diagnosis of patients in one geriatric department.

Fifty five patients between 65 and 89 years old who had their urinary problems assessed by urodynamics study were reviewed. The most common urinary symptom among males was urge incontinence, while retention and urge incontinence occurred with equal frequency among females. The commonest cause of retention in males was bladder outlet obstruction, while atonic neurogenic bladder was the most common cause in females. Urge incontinence was strongly associated with an unstable bladder, small bladder volume and Parkinson's disease. Retention of urine, and an atonic neurogenic bladder strongly correlated with diabetes mellitus. Three patients (out of 31) with unstable bladders also had detrusor external sphincter dyssynergia. Of these, two had Parkinson's disease. Although three patients were thought to have stress incontinence after history and physical examination, only two had stress incontinence with detrusor instability on urodynamic studies. The last patient had atonic bladder with overflow.

Aged↗
PubMed1991

[Involvement of the central nervous system in disseminated tuberculosis].

Four weeks after starting tuberculostatic treatment (with isoniazid, rifampicin, streptomycin and pyrazinamide) a 21-year-old man with pulmonary tuberculosis developed symptoms of a radiculomyelopathy as well as mild renal failure. After isoniazid and streptomycin had been discontinued and ethambutol and high doses of vitamin B6 had been added all signs and symptoms improved. However, 4 weeks later tuberculous meningitis occurred which at first seemed to respond to administration of 5 antituberculosis drugs and dexamethasone. But 3 weeks later the patient sustained a partial hemiparesis. Its cause was proven to be a tuberculoma in the region of the brainstem. During further administration of tuberculostatic drugs and glucocorticoids the symptoms gradually receded over 8 months. A 54-year-old man with pulmonary tuberculosis developed cranial nerve pareses and symptoms of cerebellar involvement (trunk ataxia, intention tremor, dysdiadochokinesia) 3 weeks after starting tuberculostatic treatment. Computed tomography revealed multiple intracerebral tuberculomas which gradually shrank with continuation of the tuberculostatic treatment plus glucocorticoids. These two case reports illustrate that in tuberculosis involvement of the CNS can express itself clinically through complex symptoms, sometimes even after the start of tuberculostatic treatment.

Adrenal Cortex Hormones↗
PubMed1991

Arthroscopic distension in the management of frozen shoulder.

We report a prospective study comparing the results of treatment for frozen shoulder by manipulation and physiotherapy, arthroscopic distension and physiotherapy, and physiotherapy alone in 75 patients. The first two gave better results than physiotherapy alone and we recommend arthroscopic distension as a good alternative to manipulation. It is more controllable and gives valuable information about the pathological lesions in the joint.

Adult↗
PubMed1991

Proteinase activities in bovine atrium and the possible role of mast cell tryptase in the processing of atrial natriuretic factor (ANF).

1. Using low salt, Triton X-100 and high salt extracts of bovine atria, two main proteinases were identified by means of fluorogenic oligopeptide substrates. 2. An acidic proteinase, extracted in low salt and Triton X-100 was identified as cathepsin B, but it caused little hydrolysis of the Z-Gly-Pro-Arg- containing substrate that resembles the cleavage site for activation of pro-ANF. 3. An alkaline proteinase was extracted only with high salt and had characteristics of the serine proteinase tryptase. It cleaved Z-Gly-Pro-Arg- containing substrates more efficiently than others tested and was localized in and around mast cells histochemically. Previously, Imada et al., 1988 (J. biol. Chem. 263, 9515-9519) found an identical enzyme would cleave ANF from pro-ANF. 4. These results suggest therefore that mast cell tryptase may be involved in the activation of ANF from pro-ANF.

Amino Acid Sequence↗
PubMed1990

Molecular cloning of an acrosomal sperm antigen gene and the production of its recombinant protein for immunocontraceptive vaccine.

A monoclonal antibody, HS-63, which reacts specifically with a highly conserved sperm acrosome antigen, was shown to inhibit in vitro fertilization of mouse and human. The corresponding sperm antigen designated as MSA-63 was purified to homogeneity from mouse testes and used as an immunogen to generate polyclonal antisera in rabbits. The cDNA fragments of MSA-63 gene were cloned from mouse testis cDNA library by an immunoscreening method using polyclonal antisera specific for MSA-63. Using the established cDNA clone as a probe, the gene encoding for MSA-63 protein was found to be conserved among different mammalian species. Only one specific mRNA 1.5 kb in size was identified from the adult mouse testis among different mouse tissues. The recombinant fusion protein containing MSA-63 protein fragment was produced in Escherichia coli and used to immunize female mice. Similar to the original HS-63 monoclonal antibody, the antisera thus produced reacted only with the sperm acrosome and revealed significant inhibition to the in vitro fertilization of mouse oocytes. The results of this preliminary study suggest that it is feasible to mass produce sperm-specific antigens or their antigenic fragments by recombinant DNA technology for the development of sperm antigen-based immunocontraceptive vaccines.

Acrosome↗
PubMed1990

Epidemiology of shoulder impingement in upper arm sports events.

An epidemiological survey was conducted to collect data relating to the prevalence and frequency of shoulder pain and other related problems among different athletic groups that demanded vigorous upper arm activities. A questionnaire was administered on site thus ensuring that the response rate was 100 percent. Analysis of results revealed that of the 372 respondents there were 242 male (65.1 percent) and 130 female subjects (34.9 percent), with seven (1.9 percent) above the age of 40, 119 (32 percent) between the ages of 25 and 40, and 246 (66.1 percent) below 25 years of age. A total of 163 athletes (43.8 percent) indicated that they had shoulder problems, 109 (29 percent) suffering pain. Diffuse pain was indicated by 20 respondents (5.4 percent), while localized pain during movement was reported in 89 (23.9 percent). The prevalence of shoulder pain ranked highest among volley ball players (N = 28) followed by swimmers (N = 22), while badminton, basketball and tennis participants were equally affected (N = 10).

Adult↗
PubMed1990

Use of lower limb prosthesis among elderly amputees.

Forty-seven elderly patients (21 males and 26 females) with lower limb amputation, and with prostheses fitted were studied. Their ages ranged from 65 years to 91 years old, with an average of 75.4 years. The three most common contributory causes for amputation were diabetes mellitus, vascular occlusion and carcinoma of the skin. Among the lower limb amputations, below knee amputation was the most common (93.6%). About 30% of the patients developed complications from prostheses, the 3 most common in order of frequency were stump pain, pressure ulcers and stump infection. Male patients tended to do better with prostheses than female patients. More male patients wanted prostheses for mobility, while most female patients cited cosmesis as the reason for wanting a prosthetic leg. More male patients used the prostheses more frequently and this was associated with a higher level of function in terms of self care and mobility. Reasons for non-usage of prosthesis were poor-fitting sockets, floppy stump, stump ulcers and infection. Carers of male amputees tended to cope better than those caring for female amputees. Both the present age of patient, and the age at amputation were found not to be a factor in deciding the frequency of usage of prosthesis, and the outcome of success in rehabilitation of the amputee. Psychological factors played an important role in the outcome of rehabilitation. Eighty-five percent of patients who functioned at a lower level despite a relative lack of serious medical condition cited psychological reasons for their poor performance, among which were age and the 'expected' loss of mobility with amputation.

Aged↗
PubMed1990

Infection in the elderly.

One hundred and eleven patients with pyogenic infections were studied. Of these, 32 patients (28.8%) were diabetic, and 33 patients (30%) had positive cultures obtained. Fifty-eight patients (52.3%) had fever (T degrees greater than 37.2 degrees C) while 69 patients (62.2%) had leucocytosis. Forty-one patients (36.9%) had nosocomial infections. It was found that patients older than 75 years-old did not respond to infection by a febrile response as often as those younger than 75 years-old. Mortality rate was increased in those whose T degrees greater than 38.2 degrees C and in those with more than one source of infection. Age and the presence of diabetes was not found to increase the mortality rate, though diabetics tend to have more than one source of infection. A positive blood culture was also associated with a higher mortality rate. There were also more deaths among patients with nosocomial infection than the community acquired group. The three most common sources of infection were lung, urinary tract and skin respectively. The most common group of organisms cultured was gram negative bacilli, of which Klebsiella species was most frequently isolated. Of these, 57% of the Klebsiella sp cultured came from the nosocomial group. Staphylococcus aureus was the next most frequently cultured bacteria, and all these isolates (100%) came from the nosocomial group. Though antibiotics were started within 48 hours of suspicion of infection in majority of patients (101 patients or 91%), and all of these received appropriate initial antibiotics, mortality rate remained high (26 deaths or 23.4%).

Age Factors↗
PubMed1990

Acute sympathotonic orthostatic hypotension with recovery.

We describe a 30 year-old female who presented with severe orthostatic hypotension despite appropriate compensatory tachycardia on standing, following a viral infection. Clinical assessment and laboratory evaluation failed to detect other causes of her illness besides sympathotonic orthostatic hypotension. She responded to fludrocortisone and recovered completely after 3 months. We postulate that her acute reversible illness was due to a post-viral immunological response selectively affecting the alpha adrenergic receptors subserving the post-ganglionic sympathetic vasomotor fibres.

Acute Disease↗
PubMed1989

Chromosome mapping and expression of a putative testis-determining gene in mouse.

Isolation and mapping of a mouse complementary DNA sequence (mouse Y-finger) encoding a multiple, potential zinc-binding, finger protein homologous to the candidate human testis-determining factor gene is reported. Four similar sequences were identified in Hind III-digested mouse genomic DNA. Two (7.2 and 2.0 kb) were mapped to the Y chromosome. Only the 2.0-kb fragment, however, was correlated with testis determination. Polymerase chain reaction analysis suggests both Y loci are transcribed in adult testes. A 3.6-kb fragment was mapped to the X chromosome between the T16H and T6R1 translocation breakpoints, and a fourth (6.0 kb) was mapped to chromosome 10. Hence, mYfin sequences have been duplicated several times in the mouse, although they are not duplicated in humans.

Animals↗